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Chen X, Sun F, Wang X, Feng X, Aref AR, Tian Y, Ashrafizadeh M, Wu D. Inflammation, microbiota, and pancreatic cancer. Cancer Cell Int 2025; 25:62. [PMID: 39987122 PMCID: PMC11847367 DOI: 10.1186/s12935-025-03673-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2024] [Accepted: 02/04/2025] [Indexed: 02/24/2025] Open
Abstract
Pancreatic cancer (PC) is a malignancy of gastrointestinal tract threatening the life of people around the world. In spite of the advances in the treatment of PC, the overall survival of this disease in advanced stage is less than 12%. Moreover, PC cells have aggressive behaviour in proliferation and metastasis as well as capable of developing therapy resistance. Therefore, highlighting the underlying molecular mechanisms in PC pathogenesis can provide new insights for its treatment. In the present review, inflammation and related pathways as well as role of gut microbiome in the regulation of PC pathogenesis are highlighted. The various kinds of interleukins and chemokines are able to regulate angiogenesis, metastasis, proliferation, inflammation and therapy resistance in PC cells. Furthermore, a number of molecular pathways including NF-κB, TLRs and TGF-β demonstrate dysregulation in PC aggravating inflammation and tumorigenesis. Therapeutic regulation of these pathways can reverse inflammation and progression of PC. Both chronic and acute pancreatitis have been shown to be risk factors in the development of PC, further highlighting the role of inflammation. Finally, the composition of gut microbiota can be a risk factor for PC development through affecting pathways such as NF-κB to mediate inflammation.
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Affiliation(s)
- XiaoLiang Chen
- Department of General Surgery and Integrated Traditional Chinese and Western Medicine Oncology, Tiantai People'S Hospital of Zhejiang Province(Tiantai Branch of Zhejiang Provincial People'S Hospital), Hangzhou Medical College, Taizhou, Zhejiang, China
| | - Feixia Sun
- Nursing Department, Shandong First Medical University Affiliated Occupational Disease Hospital (Shandong Provincial Occupational Disease Hospital), Jinan, China
| | - Xuqin Wang
- Department of Oncology, Chongqing General Hospital, Chongqing University, Chongqing, 401120, China
| | - Xiaoqiang Feng
- Center of Stem Cell and Regenerative Medicine, Gaozhou People's Hospital, Gaozhou, 525200, Guangdong, China
| | - Amir Reza Aref
- VitroVision Department, DeepkinetiX, Inc, Boston, MA, USA
| | - Yu Tian
- Research Center, the Huizhou Central People'S Hospital, Guangdong Medical University, Huizhou, Guangdong, China.
- School of Public Health, Benedictine University, No. 5700 College Road, Lisle, IL, 60532, USA.
| | - Milad Ashrafizadeh
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250000, Shandong, China.
| | - Dengfeng Wu
- Department of Emergency, The People'S Hospital of Gaozhou, No. 89 Xiguan Road, Gaozhou, 525200, Guangdong, China.
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Vilà-Quintana L, Fort E, Pardo L, Albiol-Quer MT, Ortiz MR, Capdevila M, Feliu A, Bahí A, Llirós M, García-Velasco A, Morell Ginestà M, Laquente B, Pozas D, Moreno V, Garcia-Gil LJ, Duell EJ, Pimenoff VN, Carreras-Torres R, Aldeguer X. Metagenomic Study Reveals Phage-Bacterial Interactome Dynamics in Gut and Oral Microbiota in Pancreatic Diseases. Int J Mol Sci 2024; 25:10988. [PMID: 39456772 PMCID: PMC11507633 DOI: 10.3390/ijms252010988] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2024] [Revised: 10/04/2024] [Accepted: 10/10/2024] [Indexed: 10/28/2024] Open
Abstract
Individuals with pancreatic-related health conditions usually show lower diversity and different composition of bacterial and viral species between the gut and oral microbiomes compared to healthy individuals. We performed a thorough microbiome analysis, using deep shotgun sequencing of stool and saliva samples obtained from patients with chronic pancreatitis (CP), pancreatic ductal adenocarcinoma (PDAC), and healthy controls (HCs).We observed similar microbiota composition at the species level in both the gut and oral samples in PDAC patients compared to HCs, among which the most distinctive finding was that the abundance of oral-originated Fusobacterium nucleatum species did not differ between the oral and the gut samples. Moreover, comparing PDAC patients with HCs, Klebsiella oxytoca was significantly more abundant in the stool samples of PDAC patients, while Streptococcus spp. showed higher abundance in both the oral and stool samples of PDAC patients. Finally, the most important finding was the distinctive gut phage-bacterial interactome pattern among PDAC patients. CrAssphages, particularly Blohavirus, showed mutual exclusion with K. oxytoca species, while Burzaovirus showed co-occurrence with Enterobacteriaceae spp., which have been shown to be capable of inducing DNA damage in human pancreatic cells ex vivo. The interactome findings warrant further mechanistic studies, as our findings may provide new insights into developing microbiota-based diagnostic and therapeutic methods for pancreatic diseases.
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Affiliation(s)
- Laura Vilà-Quintana
- Digestive Diseases and Microbiota Group, Girona Biomedical Research Institute (IDIBGI), 17190 Salt, Spain
| | - Esther Fort
- Department of Gastroenterology, Hospital Universitari de Girona Dr. Josep Trueta, 17007 Girona, Spain
| | - Laura Pardo
- Department of Gastroenterology, Hospital Universitari de Girona Dr. Josep Trueta, 17007 Girona, Spain
| | - Maria T. Albiol-Quer
- Hepato-Pancreato-Biliary Unit, Department of Surgery, Hospital Universitari de Girona Dr. Josep Trueta, 17007 Girona, Spain
| | - Maria Rosa Ortiz
- Department of Pathology, Hospital Universitari de Girona Dr. Josep Trueta, 17007 Girona, Spain
| | - Montserrat Capdevila
- Digestive Diseases and Microbiota Group, Girona Biomedical Research Institute (IDIBGI), 17190 Salt, Spain
| | - Anna Feliu
- Digestive Diseases and Microbiota Group, Girona Biomedical Research Institute (IDIBGI), 17190 Salt, Spain
| | - Anna Bahí
- Digestive Diseases and Microbiota Group, Girona Biomedical Research Institute (IDIBGI), 17190 Salt, Spain
| | - Marc Llirós
- Bioinformatics and Bioimaging (BI-SQUARED) Research Group, Biosciences Department, Faculty of Sciences, Technology and Engineering, Universitat de Vic, 08500 Vic, Spain
| | - Adelaida García-Velasco
- Precision Oncology Group, Girona Biomedical Research Institute (IDIBGI), 17190 Salt, Spain
- Institut Català d’Oncologia (ICO), Hospital Universitari de Girona Dr. Josep Trueta, 17007 Girona, Spain
| | - Mireia Morell Ginestà
- Hereditary Cancer Program, Institut Català d’Oncologia (ICO), Institut d’Investigació Biomèdica de Bellvitge (IDIBELL), CIBERONC, 08908 Barcelona, Spain
| | - Berta Laquente
- Medical Oncology Department, Institut Català d’Oncologia (ICO), Institut d’Investigació Biomèdica de Bellvitge (IDIBELL), 08908 Barcelona, Spain
| | - Débora Pozas
- Digestive Diseases and Microbiota Group, Girona Biomedical Research Institute (IDIBGI), 17190 Salt, Spain
| | - Victor Moreno
- Institut Català d’Oncologia (ICO), Institut de Recerca Biomedica de Bellvitge (IDIBELL), 08908 Barcelona, Spain
- UBICS, University of Barcelona (UB), 08028 Barcelona, Spain
- Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), 08036 Barcelona, Spain
| | - Librado Jesús Garcia-Gil
- Digestive Diseases and Microbiota Group, Girona Biomedical Research Institute (IDIBGI), 17190 Salt, Spain
| | - Eric Jeffrey Duell
- Cancer Epidemiology Research Program, Unit of Nutrition and Cancer, Institut Català d’Oncologia (ICO), Institut d’Investigació Biomèdica de Bellvitge (IDIBELL), 08908 Barcelona, Spain
| | - Ville Nikolai Pimenoff
- Department of Clinical Science, Intervention and Technology—CLINTEC, Karolinska Institutet, 14152 Stockholm, Sweden
- Unit of Population Health, Faculty of Medicine, University of Oulu, 90220 Oulu, Finland
| | - Robert Carreras-Torres
- Digestive Diseases and Microbiota Group, Girona Biomedical Research Institute (IDIBGI), 17190 Salt, Spain
| | - Xavier Aldeguer
- Digestive Diseases and Microbiota Group, Girona Biomedical Research Institute (IDIBGI), 17190 Salt, Spain
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Li S, Feng W, Wu J, Cui H, Wang Y, Liang T, An J, Chen W, Guo Z, Lei H. A Narrative Review: Immunometabolic Interactions of Host-Gut Microbiota and Botanical Active Ingredients in Gastrointestinal Cancers. Int J Mol Sci 2024; 25:9096. [PMID: 39201782 PMCID: PMC11354385 DOI: 10.3390/ijms25169096] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2024] [Revised: 08/16/2024] [Accepted: 08/18/2024] [Indexed: 09/03/2024] Open
Abstract
The gastrointestinal tract is where the majority of gut microbiota settles; therefore, the composition of the gut microbiota and the changes in metabolites, as well as their modulatory effects on the immune system, have a very important impact on the development of gastrointestinal diseases. The purpose of this article was to review the role of the gut microbiota in the host environment and immunometabolic system and to summarize the beneficial effects of botanical active ingredients on gastrointestinal cancer, so as to provide prospective insights for the prevention and treatment of gastrointestinal diseases. A literature search was performed on the PubMed database with the keywords "gastrointestinal cancer", "gut microbiota", "immunometabolism", "SCFAs", "bile acids", "polyamines", "tryptophan", "bacteriocins", "immune cells", "energy metabolism", "polyphenols", "polysaccharides", "alkaloids", and "triterpenes". The changes in the composition of the gut microbiota influenced gastrointestinal disorders, whereas their metabolites, such as SCFAs, bacteriocins, and botanical metabolites, could impede gastrointestinal cancers and polyamine-, tryptophan-, and bile acid-induced carcinogenic mechanisms. GPRCs, HDACs, FXRs, and AHRs were important receptor signals for the gut microbial metabolites in influencing the development of gastrointestinal cancer. Botanical active ingredients exerted positive effects on gastrointestinal cancer by influencing the composition of gut microbes and modulating immune metabolism. Gastrointestinal cancer could be ameliorated by altering the gut microbial environment, administering botanical active ingredients for treatment, and stimulating or blocking the immune metabolism signaling molecules. Despite extensive and growing research on the microbiota, it appeared to represent more of an indicator of the gut health status associated with adequate fiber intake than an autonomous causative factor in the prevention of gastrointestinal diseases. This study detailed the pathogenesis of gastrointestinal cancers and the botanical active ingredients used for their treatment in the hope of providing inspiration for research into simpler, safer, and more effective treatment pathways or therapeutic agents in the field.
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Affiliation(s)
- Shanlan Li
- School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 102488, China; (S.L.); (J.W.); (Y.W.); (T.L.); (J.A.); (W.C.); (Z.G.)
| | - Wuwen Feng
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China;
| | - Jiaqi Wu
- School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 102488, China; (S.L.); (J.W.); (Y.W.); (T.L.); (J.A.); (W.C.); (Z.G.)
| | - Herong Cui
- School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 102488, China; (S.L.); (J.W.); (Y.W.); (T.L.); (J.A.); (W.C.); (Z.G.)
| | - Yiting Wang
- School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 102488, China; (S.L.); (J.W.); (Y.W.); (T.L.); (J.A.); (W.C.); (Z.G.)
| | - Tianzhen Liang
- School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 102488, China; (S.L.); (J.W.); (Y.W.); (T.L.); (J.A.); (W.C.); (Z.G.)
| | - Jin An
- School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 102488, China; (S.L.); (J.W.); (Y.W.); (T.L.); (J.A.); (W.C.); (Z.G.)
| | - Wanling Chen
- School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 102488, China; (S.L.); (J.W.); (Y.W.); (T.L.); (J.A.); (W.C.); (Z.G.)
| | - Zhuoqian Guo
- School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 102488, China; (S.L.); (J.W.); (Y.W.); (T.L.); (J.A.); (W.C.); (Z.G.)
| | - Haimin Lei
- School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 102488, China; (S.L.); (J.W.); (Y.W.); (T.L.); (J.A.); (W.C.); (Z.G.)
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Aghili S, Rahimi H, Hakim LK, Karami S, Soufdoost RS, Oskouei AB, Alam M, Badkoobeh A, Golkar M, Abbasi K, Heboyan A, Hosseini ZS. Interactions Between Oral Microbiota and Cancers in the Aging Community: A Narrative Review. Cancer Control 2024; 31:10732748241270553. [PMID: 39092988 PMCID: PMC11378226 DOI: 10.1177/10732748241270553] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/04/2024] Open
Abstract
The oral microbiome potentially wields significant influence in the development of cancer. Within the human oral cavity, an impressive diversity of more than 700 bacterial species resides, making it the second most varied microbiome in the body. This finely balanced oral microbiome ecosystem is vital for sustaining oral health. However, disruptions in this equilibrium, often brought about by dietary habits and inadequate oral hygiene, can result in various oral ailments like periodontitis, cavities, gingivitis, and even oral cancer. There is compelling evidence that the oral microbiome is linked to several types of cancer, including oral, pancreatic, colorectal, lung, gastric, and head and neck cancers. This review discussed the critical connections between cancer and members of the human oral microbiota. Extensive searches were conducted across the Web of Science, Scopus, and PubMed databases to provide an up-to-date overview of our understanding of the oral microbiota's role in various human cancers. By understanding the possible microbial origins of carcinogenesis, healthcare professionals can diagnose neoplastic diseases earlier and design treatments accordingly.
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Affiliation(s)
- Sara Aghili
- Student Research Committee, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Hussein Rahimi
- Student Research Committee, School of Dentistry, Bushehr University of Medical Sciences, Bushehr, Iran
| | | | | | | | - Asal Bagherzadeh Oskouei
- Dental Research Center, Research Institute of Dental Sciences, School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mostafa Alam
- Department of Oral and Maxillofacial Surgery, School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ashkan Badkoobeh
- Department of Oral and Maxillofacial Surgery, School of Dentistry, Qom University of Medical Sciences, Qom, Iran
| | - Mohsen Golkar
- Department of Oral and Maxillofacial Surgery, School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Kamyar Abbasi
- Department of Prosthodontics, School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Artak Heboyan
- Department of Research Analytics, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India
- Department of Prosthodontics, Faculty of Stomatology, Yerevan State Medical University after Mkhitar Heratsi, Yerevan, Armenia
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Rogers S, Charles A, Thomas RM. The Prospect of Harnessing the Microbiome to Improve Immunotherapeutic Response in Pancreatic Cancer. Cancers (Basel) 2023; 15:5708. [PMID: 38136254 PMCID: PMC10741649 DOI: 10.3390/cancers15245708] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2023] [Revised: 11/24/2023] [Accepted: 12/02/2023] [Indexed: 12/24/2023] Open
Abstract
Pancreatic ductal adenocarcinoma cancer (PDAC) is projected to become the second leading cause of cancer-related death in the United States by 2030. Patients are often diagnosed with advanced disease, which explains the dismal 5-year median overall survival rate of ~12%. Immunotherapy has been successful in improving outcomes in the past decade for a variety of malignancies, including gastrointestinal cancers. However, PDAC is historically an immunologically "cold" tumor, one with an immunosuppressive environment and with restricted entry of immune cells that have limited the success of immunotherapy in these tumors. The microbiome, the intricate community of microorganisms present on and within humans, has been shown to contribute to many cancers, including PDAC. Recently, its role in tumor immunology and response to immunotherapy has generated much interest. Herein, the current state of the interaction of the microbiome and immunotherapy in PDAC is discussed with a focus on needed areas of study in order to harness the immune system to combat pancreatic cancer.
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Affiliation(s)
- Sherise Rogers
- Department of Medicine, Division of Hematology and Oncology, University of Florida College of Medicine, Gainesville, FL 32610, USA;
| | - Angel Charles
- Department of Surgery, University of Florida College of Medicine, Gainesville, FL 32610, USA;
| | - Ryan M. Thomas
- Department of Surgery, University of Florida College of Medicine, Gainesville, FL 32610, USA;
- Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, FL 32603, USA
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Asili P, Mirahmad M, Rezaei P, Mahdavi M, Larijani B, Tavangar SM. The Association of Oral Microbiome Dysbiosis with Gastrointestinal Cancers and Its Diagnostic Efficacy. J Gastrointest Cancer 2023; 54:1082-1101. [PMID: 36600023 DOI: 10.1007/s12029-022-00901-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/15/2022] [Indexed: 01/06/2023]
Abstract
BACKGROUND The second leading mortality cause in the world is cancer, making it a critical issue that impacts human health. As a result, scientists are looking for novel biomarkers for cancer detection. The oral microbiome, made up of approximately 700 species-level taxa, is a significant source for discovering novel biomarkers. In this review, we aimed to prepare a summary of research that has investigated the association between the oral microbiome and gastrointestinal cancers. METHODS We searched online scientific datasets including Web of Science, PubMed, Scopus, and Google Scholar. Eligibility criteria included human studies that reported abundances of the oral microbiome, or its diagnostic/prognostic performance in patients with gastrointestinal cancers. RESULTS Some phyla of the oral microbiome have a relationship with cancers. Some particular phyla of the oral microbiome that may be related to gastrointestinal cancers consist of Firmicutes, Actinobacteria, Bacteroidetes, Proteobacteria, and Fusobacteria. Changes in the abundances of Porphyromonas, Fusobacterium, Prevotella, and Veillonella are correlated with carcinogenesis, and may be used for distinguishing cancer patients from healthy subjects. Oral, colorectal, pancreatic, and esophageal cancers are the most important cancers related to the oral microbiome. CONCLUSION The results of this study may help future research to select bacteria as an early diagnostic or prognostic biomarker of gastrointestinal cancer. Given the current state of our knowledge, additional research is required to comprehend the multiplex processes underlying the role of bacterial microbiota upon cancer progression and to characterize the complex microbiota-host interaction network.
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Affiliation(s)
- Pooria Asili
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Maryam Mirahmad
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Parisa Rezaei
- Department of Nutrition, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Mohammad Mahdavi
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Bagher Larijani
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Seyed Mohammad Tavangar
- Chronic Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
- Department of Pathology, Dr. Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
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Meslier V, Menozzi E, David A, Morabito C, Lucas Del Pozo S, Famechon A, North J, Quinquis B, Koletsi S, Macnaughtan J, Mezabrovschi R, Ehrlich SD, Schapira AHV, Almeida M. Evaluation of an Adapted Semi-Automated DNA Extraction for Human Salivary Shotgun Metagenomics. Biomolecules 2023; 13:1505. [PMID: 37892187 PMCID: PMC10604855 DOI: 10.3390/biom13101505] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2023] [Revised: 09/29/2023] [Accepted: 10/05/2023] [Indexed: 10/29/2023] Open
Abstract
Recent attention has highlighted the importance of oral microbiota in human health and disease, e.g., in Parkinson's disease, notably using shotgun metagenomics. One key aspect for efficient shotgun metagenomic analysis relies on optimal microbial sampling and DNA extraction, generally implementing commercial solutions developed to improve sample collection and preservation, and provide high DNA quality and quantity for downstream analysis. As metagenomic studies are today performed on a large number of samples, the next evolution to increase study throughput is with DNA extraction automation. In this study, we proposed a semi-automated DNA extraction protocol for human salivary samples collected with a commercial kit, and compared the outcomes with the DNA extraction recommended by the manufacturer. While similar DNA yields were observed between the protocols, our semi-automated DNA protocol generated significantly higher DNA fragment sizes. Moreover, we showed that the oral microbiome composition was equivalent between DNA extraction methods, even at the species level. This study demonstrates that our semi-automated protocol is suitable for shotgun metagenomic analysis, while allowing for improved sample treatment logistics with reduced technical variability and without compromising the structure of the oral microbiome.
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Affiliation(s)
- Victoria Meslier
- MetaGenoPolis, INRAE, Université Paris-Saclay, 78350 Jouy-en-Josas, France (C.M.)
- Aligning Science Across Parkinson’s (ASAP) Collaborative Research Network, Chevy Chase, MD 20815, USA (S.K.); (R.M.); (S.D.E.)
| | - Elisa Menozzi
- Aligning Science Across Parkinson’s (ASAP) Collaborative Research Network, Chevy Chase, MD 20815, USA (S.K.); (R.M.); (S.D.E.)
- Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London (UCL), London WC1E 6BT, UK
| | - Aymeric David
- MetaGenoPolis, INRAE, Université Paris-Saclay, 78350 Jouy-en-Josas, France (C.M.)
- Aligning Science Across Parkinson’s (ASAP) Collaborative Research Network, Chevy Chase, MD 20815, USA (S.K.); (R.M.); (S.D.E.)
| | - Christian Morabito
- MetaGenoPolis, INRAE, Université Paris-Saclay, 78350 Jouy-en-Josas, France (C.M.)
- Aligning Science Across Parkinson’s (ASAP) Collaborative Research Network, Chevy Chase, MD 20815, USA (S.K.); (R.M.); (S.D.E.)
| | - Sara Lucas Del Pozo
- Aligning Science Across Parkinson’s (ASAP) Collaborative Research Network, Chevy Chase, MD 20815, USA (S.K.); (R.M.); (S.D.E.)
- Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London (UCL), London WC1E 6BT, UK
| | - Alexandre Famechon
- MetaGenoPolis, INRAE, Université Paris-Saclay, 78350 Jouy-en-Josas, France (C.M.)
- Aligning Science Across Parkinson’s (ASAP) Collaborative Research Network, Chevy Chase, MD 20815, USA (S.K.); (R.M.); (S.D.E.)
| | - Janet North
- Research Department of Hematology, Cancer Institute, University College London (UCL), London WC1E 6BT, UK
| | - Benoit Quinquis
- MetaGenoPolis, INRAE, Université Paris-Saclay, 78350 Jouy-en-Josas, France (C.M.)
- Aligning Science Across Parkinson’s (ASAP) Collaborative Research Network, Chevy Chase, MD 20815, USA (S.K.); (R.M.); (S.D.E.)
| | - Sofia Koletsi
- Aligning Science Across Parkinson’s (ASAP) Collaborative Research Network, Chevy Chase, MD 20815, USA (S.K.); (R.M.); (S.D.E.)
- Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London (UCL), London WC1E 6BT, UK
| | - Jane Macnaughtan
- Aligning Science Across Parkinson’s (ASAP) Collaborative Research Network, Chevy Chase, MD 20815, USA (S.K.); (R.M.); (S.D.E.)
- Liver Failure Group, Institute for Liver and Digestive Health, University College London, London WC1E 6BT, UK
| | - Roxana Mezabrovschi
- Aligning Science Across Parkinson’s (ASAP) Collaborative Research Network, Chevy Chase, MD 20815, USA (S.K.); (R.M.); (S.D.E.)
- Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London (UCL), London WC1E 6BT, UK
| | - S. Dusko Ehrlich
- Aligning Science Across Parkinson’s (ASAP) Collaborative Research Network, Chevy Chase, MD 20815, USA (S.K.); (R.M.); (S.D.E.)
- Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London (UCL), London WC1E 6BT, UK
| | - Anthony H. V. Schapira
- Aligning Science Across Parkinson’s (ASAP) Collaborative Research Network, Chevy Chase, MD 20815, USA (S.K.); (R.M.); (S.D.E.)
- Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London (UCL), London WC1E 6BT, UK
| | - Mathieu Almeida
- MetaGenoPolis, INRAE, Université Paris-Saclay, 78350 Jouy-en-Josas, France (C.M.)
- Aligning Science Across Parkinson’s (ASAP) Collaborative Research Network, Chevy Chase, MD 20815, USA (S.K.); (R.M.); (S.D.E.)
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Daneste H, Mohammadzadeh Boukani L, Ramezani N, Asadi F, Zaidan HK, Sadeghzade A, Ehsannia M, Azarashk A, Gholizadeh N. Combination therapy along with mesenchymal stem cells in wound healing; the state of the art. Adv Med Sci 2023; 68:441-449. [PMID: 37924749 DOI: 10.1016/j.advms.2023.10.006] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2023] [Revised: 06/23/2023] [Accepted: 10/17/2023] [Indexed: 11/06/2023]
Abstract
Mesenchymal stem cells (MSCs) are being increasingly used in various therapeutic applications including skin tissue repair and wound healing. The positive effects of the MSCs therapy are largely elicited by immunomodulation, increasing angiogenesis, supporting extracellular matrix (ECM) and thus favoring skin structure. However, the therapeutic competences of MSC-based therapies are somewhat hindered by their apparent modest clinical merits, conferring the need for methods that would rise the efficacy of such therapies. A plethora of reports have shown that therapeutic properties of MSCs could be enhanced with other strategies and compounds like biomaterial and platelet-rich plasma (PRP) to target key possessions of MSCs and properties of adjacent tissues concurrently. Manipulation of cellular stress-response mechanisms to improve cell resistance to oxidative stress prior to or during MSC injection could also improve therapeutic efficacy of MSCs. In the current review, we shed light on the recent advances in MSCs combination therapy with other ingredients and procedures to sustain MSCs-mediated effects in wound healing.
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Affiliation(s)
- Hossein Daneste
- Department of Oral and Maxillofacial Surgery, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran
| | | | - Narges Ramezani
- Department of Biology, Damghan Branch, Islamic Azad University, Damghan, Iran
| | - Fatemeh Asadi
- Department of Genetics, Izeh Branch, Islamic Azad University, Izeh, Iran
| | - Haider Kamil Zaidan
- Department of Medical Laboratories Techniques, Al-Mustaqbal University College, Hillah, Babylon, Iraq
| | - Azita Sadeghzade
- Department of Oral and Maxillofacial Medicine, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Maedeh Ehsannia
- Faculty of Basic Sciences, Islamic Azad University, Tehran East Branch, Tehran, Iran
| | - Ali Azarashk
- Department of Pharmaceutics, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
| | - Nasim Gholizadeh
- Department of Dermatology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
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9
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Bangolo AI, Trivedi C, Jani I, Pender S, Khalid H, Alqinai B, Intisar A, Randhawa K, Moore J, De Deugd N, Faisal S, Suresh SB, Gopani P, Nagesh VK, Proverbs-Singh T, Weissman S. Impact of gut microbiome in the development and treatment of pancreatic cancer: Newer insights. World J Gastroenterol 2023; 29:3984-3998. [PMID: 37476590 PMCID: PMC10354587 DOI: 10.3748/wjg.v29.i25.3984] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Revised: 05/24/2023] [Accepted: 06/12/2023] [Indexed: 06/28/2023] Open
Abstract
The gut microbiome plays an important role in the variation of pharmacologic response. This aspect is especially important in the era of precision medicine, where understanding how and to what extent the gut microbiome interacts with drugs and their actions will be key to individualizing therapy. The impact of the composition of the gut microbiome on the efficacy of newer cancer therapies such as immune checkpoint inhibitors and chimeric antigen receptor T-cell treatment has become an active area of research. Pancreatic adenocarcinoma (PAC) has a poor prognosis even in those with potentially resectable disease, and treatment options are very limited. Newer studies have concluded that there is a synergistic effect for immunotherapy in combination with cytotoxic drugs, in the treatment of PAC. A variety of commensal microbiota can affect the efficacy of conventional chemotherapy and immunotherapy by modulating the tumor microenvironment in the treatment of PAC. This review will provide newer insights on the impact that alterations made in the gut microbial system have in the development and treatment of PAC.
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Affiliation(s)
- Ayrton I Bangolo
- Department of Internal Medicine, Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Chinmay Trivedi
- Department of Internal Medicine, Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Ishan Jani
- Department of Internal Medicine, Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Silvanna Pender
- Department of Internal Medicine, Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Hirra Khalid
- Department of Internal Medicine, Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Budoor Alqinai
- Department of Internal Medicine, Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Alina Intisar
- Department of Internal Medicine, Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Karamvir Randhawa
- Department of Internal Medicine, Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Joseph Moore
- Department of Internal Medicine, Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Nicoleta De Deugd
- Department of Internal Medicine, Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Shaji Faisal
- Department of Internal Medicine, Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Suchith Boodgere Suresh
- Department of Internal Medicine, Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Parva Gopani
- Department of Internal Medicine, Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Vignesh K Nagesh
- Department of Internal Medicine, Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Tracy Proverbs-Singh
- Department of Gastrointestinal Malignancies, John Theurer Cancer Center, Hackensack, NJ 07601, United States
| | - Simcha Weissman
- Department of Internal Medicine, Palisades Medical Center, North Bergen, NJ 07047, United States
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10
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Chai Y, Huang Z, Shen X, Lin T, Zhang Y, Feng X, Mao Q, Liang Y. Microbiota Regulates Pancreatic Cancer Carcinogenesis through Altered Immune Response. Microorganisms 2023; 11:1240. [PMID: 37317214 PMCID: PMC10221276 DOI: 10.3390/microorganisms11051240] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2023] [Revised: 05/02/2023] [Accepted: 05/04/2023] [Indexed: 06/16/2023] Open
Abstract
The microbiota is present in many parts of the human body and plays essential roles. The most typical case is the occurrence and development of cancer. Pancreatic cancer (PC), one of the most aggressive and lethal types of cancer, has recently attracted the attention of researchers. Recent research has revealed that the microbiota regulates PC carcinogenesis via an altered immune response. Specifically, the microbiota, in several sites, including the oral cavity, gastrointestinal tract, and pancreatic tissue, along with the numerous small molecules and metabolites it produces, influences cancer progression and treatment by activating oncogenic signaling, enhancing oncogenic metabolic pathways, altering cancer cell proliferation, and triggering chronic inflammation that suppresses tumor immunity. Diagnostics and treatments based on or in combination with the microbiota offer novel insights to improve efficiency compared with existing therapies.
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Affiliation(s)
- Yihan Chai
- Department of General Surgery, Zhejiang University School of Medicine, Sir Run Run Shaw Hospital, Hangzhou 310016, China
| | - Zhengze Huang
- Department of General Surgery, Zhejiang University School of Medicine, Sir Run Run Shaw Hospital, Hangzhou 310016, China
| | - Xuqiu Shen
- Department of General Surgery, Zhejiang University School of Medicine, Sir Run Run Shaw Hospital, Hangzhou 310016, China
| | - Tianyu Lin
- Department of General Surgery, Zhejiang University School of Medicine, Sir Run Run Shaw Hospital, Hangzhou 310016, China
| | - Yiyin Zhang
- Department of General Surgery, Zhejiang University School of Medicine, Sir Run Run Shaw Hospital, Hangzhou 310016, China
| | - Xu Feng
- Department of General Surgery, Zhejiang University School of Medicine, Sir Run Run Shaw Hospital, Hangzhou 310016, China
| | - Qijiang Mao
- Department of General Surgery, Zhejiang University School of Medicine, Sir Run Run Shaw Hospital, Hangzhou 310016, China
- Zhejiang Provincial Key Laboratory of Laparoscopic Technology, Hangzhou 310016, China
- Zhejiang Province Medical Research Center of Minimally Invasive Diagnosis and Treatment of Abdominal Diseases, Hangzhou 310028, China
| | - Yuelong Liang
- Department of General Surgery, Zhejiang University School of Medicine, Sir Run Run Shaw Hospital, Hangzhou 310016, China
- Zhejiang Province Medical Research Center of Minimally Invasive Diagnosis and Treatment of Abdominal Diseases, Hangzhou 310028, China
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11
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Ge Y, Sun F, Zhao B, Kong F, Li Z, Kong X. Bacteria derived extracellular vesicles in the pathogenesis and treatment of gastrointestinal tumours. Front Oncol 2023; 12:1103446. [PMID: 36776356 PMCID: PMC9910087 DOI: 10.3389/fonc.2022.1103446] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2022] [Accepted: 12/28/2022] [Indexed: 01/27/2023] Open
Abstract
Extracellular vesicles are fundamentally significant in the communication between cells. Outer Membrane Vesicles(OMVs) are a special kind of EVs produced by Gram-negative bacteria, which are minute exosome-like particles budding from the outer membrane, which have been found to play essential roles in diverse bacterial life events, including regulation of microbial interactions, pathogenesis promotion, stress responses and biofilm formation. Recently, and more researches have explored the substantial potentials of EVs as natural functional nanoparticles in the bioengineering applications in infectious diseases, cardiovascular diseases, autoimmune diseases and neurological diseases, such as antibacterial therapy, cancer drugs and immunoadjuvants, with several candidates in clinical trials showing promising efficacy. However, due to the poor understanding of sources, membrane structures and biogenesis mechanisms of EVs, progress in clinical applications still remains timid. In this review, we summarize the latest findings of EVs, especially in gastrointestinal tract tumours, to provide a comprehensive introduction of EVs in tumorigenesis and therapeutics.
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Affiliation(s)
- Yang Ge
- Changhai Clinical Research Unit, Changhai Hospital, Naval Military Medical University, Shanghai, China,Department of Gastroenterology, Changhai Hospital, Naval Military Medical University, Shanghai, China
| | - Fengyuan Sun
- Changhai Clinical Research Unit, Changhai Hospital, Naval Military Medical University, Shanghai, China
| | - Bo Zhao
- Changhai Clinical Research Unit, Changhai Hospital, Naval Military Medical University, Shanghai, China
| | - Fanyang Kong
- Changhai Clinical Research Unit, Changhai Hospital, Naval Military Medical University, Shanghai, China,Department of Gastroenterology, Changhai Hospital, Naval Military Medical University, Shanghai, China,*Correspondence: Xiangyu Kong, ; Zhaoshen Li, ; Fanyang Kong,
| | - Zhaoshen Li
- Changhai Clinical Research Unit, Changhai Hospital, Naval Military Medical University, Shanghai, China,*Correspondence: Xiangyu Kong, ; Zhaoshen Li, ; Fanyang Kong,
| | - Xiangyu Kong
- Changhai Clinical Research Unit, Changhai Hospital, Naval Military Medical University, Shanghai, China,Department of Gastroenterology, Changhai Hospital, Naval Military Medical University, Shanghai, China,National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, Shanghai, China,*Correspondence: Xiangyu Kong, ; Zhaoshen Li, ; Fanyang Kong,
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12
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Tong F, Wang P, Chen Z, Liu Y, Wang L, Guo J, Li Z, Cai H, Wei J. Combined Ferromagnetic Nanoparticles for Effective Periodontal Biofilm Eradication in Rat Model. Int J Nanomedicine 2023; 18:2371-2388. [PMID: 37192894 PMCID: PMC10182795 DOI: 10.2147/ijn.s402410] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2023] [Accepted: 04/26/2023] [Indexed: 05/18/2023] Open
Abstract
Introduction The critical challenge for periodontitis therapy is thoroughly eliminating the dental plaque biofilm, particularly penetrating the deep periodontal tissue. Regular therapeutic strategies are insufficient to penetrate the plaque without disturbing the commensal microflora of the oral cavity. Here, we constructed a Fe3O4 magnetic nanoparticle loading minocycline (FPM NPs) to penetrate the biofilm physically and effectively eliminate periodontal biofilm. Methods In order to penetrate and remove the biofilm effectively, Fe3O4 magnetic nanoparticles were modified with minocycline using a co-precipitation method. The particle size and dispersion of the nanoparticles were characterized by transmission electron microscopy, scanning electron microscopy, and dynamic light scattering. The antibacterial effects were examined to verify the magnetic targeting of FPM NPs. Confocal laser scanning microscopy was employed to check the effect of FPM + MF and develop the best FPM NPs treatment strategy. Additionally, the therapeutic effect of FPM NPs was investigated in periodontitis rat models. The expression of IL-1β, IL-6, and TNF-α in periodontal tissues was measured by qRT-PCR and Western blot. Results The multifunctional nanoparticles exhibited intense anti-biofilm activity and good biocompatibility. The magnetic forces could pull FMP NPs against the biofilm mass and kill bacteria deep in the biofilms both in vivo and in vitro. The integrity of the bacterial biofilm is disrupted under the motivation of the magnetic field, allowing for improved drug penetration and antibacterial performance. The periodontal inflammation recovered well after FPM NPs treatment in rat models. Furthermore, FPM NPs could be monitored in real-time and have magnetic targeting potentials. Conclusion FPM NPs exhibit good chemical stability and biocompatibility. The novel nanoparticle presents a new approach for treating periodontitis and provides experimental support for using magnetic-targeted nanoparticles in clinic applications.
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Affiliation(s)
- Fei Tong
- School of Stomatology, Nanchang University, Nanchang, 330006, People’s Republic of China
- School of Chemistry and Chemical Engineering, Nanchang University, Nanchang, Jiangxi Province, 330031, People’s Republic of China
- The Key Laboratory of Oral Biomedicine, Nanchang, Jiangxi Province, 330006, People’s Republic of China
- Jiangxi Province Clinical Research Center for Oral Diseases, Nanchang, 330006, People’s Republic of China
| | - Pei Wang
- School of Stomatology, Nanchang University, Nanchang, 330006, People’s Republic of China
- The Key Laboratory of Oral Biomedicine, Nanchang, Jiangxi Province, 330006, People’s Republic of China
- Jiangxi Province Clinical Research Center for Oral Diseases, Nanchang, 330006, People’s Republic of China
| | - Ziqiang Chen
- School of Stomatology, Nanchang University, Nanchang, 330006, People’s Republic of China
- The Key Laboratory of Oral Biomedicine, Nanchang, Jiangxi Province, 330006, People’s Republic of China
- Jiangxi Province Clinical Research Center for Oral Diseases, Nanchang, 330006, People’s Republic of China
| | - Yifan Liu
- School of Stomatology, Nanchang University, Nanchang, 330006, People’s Republic of China
- The Key Laboratory of Oral Biomedicine, Nanchang, Jiangxi Province, 330006, People’s Republic of China
- Jiangxi Province Clinical Research Center for Oral Diseases, Nanchang, 330006, People’s Republic of China
| | - Lianguo Wang
- School of Stomatology, Nanchang University, Nanchang, 330006, People’s Republic of China
- The Key Laboratory of Oral Biomedicine, Nanchang, Jiangxi Province, 330006, People’s Republic of China
- Jiangxi Province Clinical Research Center for Oral Diseases, Nanchang, 330006, People’s Republic of China
| | - Jun Guo
- School of Stomatology, Nanchang University, Nanchang, 330006, People’s Republic of China
- The Key Laboratory of Oral Biomedicine, Nanchang, Jiangxi Province, 330006, People’s Republic of China
- Jiangxi Province Clinical Research Center for Oral Diseases, Nanchang, 330006, People’s Republic of China
| | - Zhihua Li
- School of Stomatology, Nanchang University, Nanchang, 330006, People’s Republic of China
- The Key Laboratory of Oral Biomedicine, Nanchang, Jiangxi Province, 330006, People’s Republic of China
- Jiangxi Province Clinical Research Center for Oral Diseases, Nanchang, 330006, People’s Republic of China
| | - Hu Cai
- School of Chemistry and Chemical Engineering, Nanchang University, Nanchang, Jiangxi Province, 330031, People’s Republic of China
- Jiangxi Province Clinical Research Center for Oral Diseases, Nanchang, 330006, People’s Republic of China
- Correspondence: Hu Cai, School of Chemistry and Chemical Engineering, Nanchang University, 999# Xuefu Road, Honggutan District, Nanchang, Jiangxi, 330031, People’s Republic of China, Tel +86 791 83969514, Email
| | - Junchao Wei
- School of Stomatology, Nanchang University, Nanchang, 330006, People’s Republic of China
- School of Chemistry and Chemical Engineering, Nanchang University, Nanchang, Jiangxi Province, 330031, People’s Republic of China
- The Key Laboratory of Oral Biomedicine, Nanchang, Jiangxi Province, 330006, People’s Republic of China
- Jiangxi Province Clinical Research Center for Oral Diseases, Nanchang, 330006, People’s Republic of China
- Junchao Wei, School of Stomatology, Nanchang University, 49# Fuzhou Road, Donghu District, Nanchang, Jiangxi, 330006, People’s Republic of China, Tel +86 791 86236950, +86 791 6361141, Email
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13
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Binda C, Gibiino G, Sbrancia M, Coluccio C, Cazzato M, Carloni L, Cucchetti A, Ercolani G, Sambri V, Fabbri C. Microbiota in the Natural History of Pancreatic Cancer: From Predisposition to Therapy. Cancers (Basel) 2022; 15:cancers15010001. [PMID: 36611999 PMCID: PMC9817971 DOI: 10.3390/cancers15010001] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2022] [Revised: 11/28/2022] [Accepted: 12/13/2022] [Indexed: 12/29/2022] Open
Abstract
Early microbiome insights came from gut microbes and their role among intestinal and extraintestinal disease. The latest evidence suggests that the microbiota is a true organ, capable of several interactions throughout the digestive system, attracting specific interest in the biliopancreatic district. Despite advances in diagnostics over the last few decades and improvements in the management of this disease, pancreatic cancer is still a common cause of cancer death. Microbiota can influence the development of precancerous disease predisposing to pancreatic cancer (PC). At the same time, neoplastic tissue shows specific characteristics in terms of diversity and phenotype, determining the short- and long-term prognosis. Considering the above information, a role for microbiota has also been hypothesized in the different phases of the PC approach, providing future revolutionary therapeutic insights. Microbiota-modulating therapies could open new issues in the therapeutic landscape. The aim of this narrative review is to assess the most updated evidence on microbiome in all the steps regarding pancreatic adenocarcinoma, from early development to response to antineoplastic therapy and long-term prognosis.
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Affiliation(s)
- Cecilia Binda
- Gastroenterology and Digestive Endoscopy Unit, Forlì-Cesena Hospitals, Ausl Romagna, 47121 Forlì-Cesena, Italy
| | - Giulia Gibiino
- Gastroenterology and Digestive Endoscopy Unit, Forlì-Cesena Hospitals, Ausl Romagna, 47121 Forlì-Cesena, Italy
- Correspondence: ; Tel.: +39-3488609557
| | - Monica Sbrancia
- Gastroenterology and Digestive Endoscopy Unit, Forlì-Cesena Hospitals, Ausl Romagna, 47121 Forlì-Cesena, Italy
| | - Chiara Coluccio
- Gastroenterology and Digestive Endoscopy Unit, Forlì-Cesena Hospitals, Ausl Romagna, 47121 Forlì-Cesena, Italy
| | - Maria Cazzato
- Gastroenterology and Digestive Endoscopy Unit, Forlì-Cesena Hospitals, Ausl Romagna, 47121 Forlì-Cesena, Italy
| | - Lorenzo Carloni
- Gastroenterology and Digestive Endoscopy Unit, Forlì-Cesena Hospitals, Ausl Romagna, 47121 Forlì-Cesena, Italy
- Department of Medical and Surgical Sciences—DIMEC, Alma Mater Studiorum, University of Bologna, 40138 Bologna, Italy
| | - Alessandro Cucchetti
- Department of Medical and Surgical Sciences—DIMEC, Alma Mater Studiorum, University of Bologna, 40138 Bologna, Italy
- General and Oncologic Surgery, Morgagni—Pierantoni Hospital, AUSL Romagna, 47121 Forlì, Italy
| | - Giorgio Ercolani
- Department of Medical and Surgical Sciences—DIMEC, Alma Mater Studiorum, University of Bologna, 40138 Bologna, Italy
- General and Oncologic Surgery, Morgagni—Pierantoni Hospital, AUSL Romagna, 47121 Forlì, Italy
| | - Vittorio Sambri
- Department of Medical and Surgical Sciences—DIMEC, Alma Mater Studiorum, University of Bologna, 40138 Bologna, Italy
- Microbiology Unit, Hub Laboratory, AUSL della Romagna, 47121 Cesena, Italy
| | - Carlo Fabbri
- Gastroenterology and Digestive Endoscopy Unit, Forlì-Cesena Hospitals, Ausl Romagna, 47121 Forlì-Cesena, Italy
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14
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Factors that influence the pancreatic and duodenal microbiome in patients undergoing pancreatic surgery. PLoS One 2022; 17:e0278377. [PMID: 36525425 PMCID: PMC9757549 DOI: 10.1371/journal.pone.0278377] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2022] [Accepted: 11/15/2022] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND/OBJECTIVES This study examined the correlation between pancreatic microbiome and patients characteristics. Furthermore, we compared different duodenal materials to examine their reflection of the pancreatic microbiome. METHODS Patients undergoing pancreatic surgery were included in the study. Characteristics of those patients were prospectively registered and sterile pancreatic biopsies were collected during surgery. After completion of the resection, duodenal fluid, -tissue and -swab were collected. Bacterial DNA was extracted and analyzed with IS-pro assay. RESULTS Paired samples of 51 patients were available for evaluation, including pancreatic biopsies from all patients, 22 duodenal fluids, 21 duodenal swabs and 11 duodenal tissues. The pancreatic microbiome consisted mostly of Proteobacteria followed by Firmicutes, Actinobacteria, Fusobacteria and Verrucomicrobia (FAFV) and Bacteroidetes. On species level, Enterococcus faecalis, Escherichia coli, and Enterobacter-Klebsiella were most abundant. In pancreatic biopsies, the total bacterial load and Proteobacteria load were significantly higher in patients with biliary drainage (54618.0 vs 5623.5; 9119.0 vs 2067.1). Patients who used proton pump inhibitors had a significantly higher total bacterial load (115964.7 vs 8495.8), more FAFV (66862.9 vs 1890.1), more Proteobacteria (24245.9 vs 2951.4) and more Bacteroidetes (542.5 vs 25.8). The head of the pancreas contained significantly more bacteria (21193.4 vs 2096.8) and more FAFV (5225.7 vs 19.0) compared to the tail, regardless of biliary drainage. Furthermore, the microbiome of all duodenal materials showed a weak correlation with the pancreatic microbiome. CONCLUSION Biliary drainage, use of proton pump inhibitors, and anatomic location of the pancreatic biopsy influence the pancreatic microbiome. Furthermore, the duodenal microbiome does not suffice as a surrogate for the pancreatic microbiome.
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15
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Herremans KM, Riner AN, Cameron ME, McKinley KL, Triplett EW, Hughes SJ, Trevino JG. The oral microbiome, pancreatic cancer and human diversity in the age of precision medicine. MICROBIOME 2022; 10:93. [PMID: 35701831 PMCID: PMC9199224 DOI: 10.1186/s40168-022-01262-7] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/26/2021] [Accepted: 03/23/2022] [Indexed: 05/09/2023]
Abstract
Pancreatic cancer is a deadly disease with limited diagnostic and treatment options. Not all populations are affected equally, as disparities exist in pancreatic cancer prevalence, treatment and outcomes. Recently, next-generation sequencing has facilitated a more comprehensive analysis of the human oral microbiome creating opportunity for its application in precision medicine. Oral microbial shifts occur in patients with pancreatic cancer, which may be appreciated years prior to their diagnosis. In addition, pathogenic bacteria common in the oral cavity have been found within pancreatic tumors. Despite these findings, much remains unknown about how or why the oral microbiome differs in patients with pancreatic cancer. As individuals develop, their oral microbiome reflects both their genotype and environmental influences. Genetics, race/ethnicity, smoking, socioeconomics and age affect the composition of the oral microbiota, which may ultimately play a role in pancreatic carcinogenesis. Multiple mechanisms have been proposed to explain the oral dysbiosis found in patients with pancreatic cancer though they have yet to be confirmed. With a better understanding of the interplay between the oral microbiome and pancreatic cancer, improved diagnostic and therapeutic approaches may be implemented to reduce healthcare disparities. Video Abstract.
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Affiliation(s)
- Kelly M. Herremans
- Department of Surgery, University of Florida College of Medicine, P.O. Box 100286, Gainesville, FL 32610 USA
| | - Andrea N. Riner
- Department of Surgery, University of Florida College of Medicine, P.O. Box 100286, Gainesville, FL 32610 USA
| | - Miles E. Cameron
- Department of Surgery, University of Florida College of Medicine, P.O. Box 100286, Gainesville, FL 32610 USA
| | - Kelley L. McKinley
- Department of Microbiology and Cell Science, University of Florida, P.O. Box 110700, Gainesville, FL 32611-0700 USA
| | - Eric W. Triplett
- Department of Microbiology and Cell Science, University of Florida, P.O. Box 110700, Gainesville, FL 32611-0700 USA
| | - Steven J. Hughes
- Department of Surgery, University of Florida College of Medicine, P.O. Box 100286, Gainesville, FL 32610 USA
| | - Jose G. Trevino
- Division of Surgical Oncology, Virginia Commonwealth University, 1200 E Broad St, Richmond, VA 23298-0645 USA
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16
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Sexton RE, Uddin MH, Bannoura S, Khan HY, Mzannar Y, Li Y, Aboukameel A, Al-Hallak MN, Al-Share B, Mohamed A, Nagasaka M, El-Rayes B, Azmi AS. Connecting the Human Microbiome and Pancreatic Cancer. Cancer Metastasis Rev 2022; 41:317-331. [PMID: 35366155 PMCID: PMC8976105 DOI: 10.1007/s10555-022-10022-w] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2022] [Accepted: 03/02/2022] [Indexed: 11/02/2022]
Abstract
Pancreatic cancer is a deadly disease that is increasing in incidence throughout the world. There are no clear causal factors associated with the incidence of pancreatic cancer; however, some correlation to smoking, diabetes and alcohol has been described. Recently, a few studies have linked the human microbiome (oral and gastrointestinal tract) to pancreatic cancer development. A perturbed microbiome has been shown to alter normal cells while promoting cancer-related processes such as increased cell signaling, immune system evasion and invasion. In this article, we will review in detail the alterations within the gut and oral microbiome that have been linked to pancreatic cancer and explore the ability of other microbiomes, such as the lung and skin microbiome, to contribute to disease development. Understanding ways to identify a perturbed microbiome can result in advancements in pancreatic cancer research and allow for prevention, earlier detection and alternative treatment strategies for patients.
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Affiliation(s)
- Rachel E Sexton
- Department of Oncology, Wayne State University School of Medicine, Karmanos Cancer Institute, 4100 John R, Detroit, MI, 48201, USA
| | - Md Hafiz Uddin
- Department of Oncology, Wayne State University School of Medicine, Karmanos Cancer Institute, 4100 John R, Detroit, MI, 48201, USA
| | - Sahar Bannoura
- Department of Oncology, Wayne State University School of Medicine, Karmanos Cancer Institute, 4100 John R, Detroit, MI, 48201, USA
| | - Husain Yar Khan
- Department of Oncology, Wayne State University School of Medicine, Karmanos Cancer Institute, 4100 John R, Detroit, MI, 48201, USA
| | - Yousef Mzannar
- Department of Oncology, Wayne State University School of Medicine, Karmanos Cancer Institute, 4100 John R, Detroit, MI, 48201, USA
| | - Yiwei Li
- Department of Oncology, Wayne State University School of Medicine, Karmanos Cancer Institute, 4100 John R, Detroit, MI, 48201, USA
| | - Amro Aboukameel
- Department of Oncology, Wayne State University School of Medicine, Karmanos Cancer Institute, 4100 John R, Detroit, MI, 48201, USA
| | - Mohammad Najeeb Al-Hallak
- Department of Oncology, Wayne State University School of Medicine, Karmanos Cancer Institute, 4100 John R, Detroit, MI, 48201, USA
| | - Bayan Al-Share
- Department of Oncology, Wayne State University School of Medicine, Karmanos Cancer Institute, 4100 John R, Detroit, MI, 48201, USA
| | - Amr Mohamed
- UH Seidman Cancer Center, University Hospitals, Case Western Reserve University, Cleveland, OH, USA
- Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, USA
| | - Misako Nagasaka
- University of California, Irvine, UCI Health Chao Family Comprehensive Cancer Center, CA, Irvine, USA
| | - Bassel El-Rayes
- O'Neal Comprehensive Cancer Center, University of Alabama, AL, Tuscaloosa, USA
| | - Asfar S Azmi
- Department of Oncology, Wayne State University School of Medicine, Karmanos Cancer Institute, 4100 John R, Detroit, MI, 48201, USA.
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Liu J, Zhang Y. Intratumor microbiome in cancer progression: current developments, challenges and future trends. Biomark Res 2022; 10:37. [PMID: 35642013 PMCID: PMC9153132 DOI: 10.1186/s40364-022-00381-5] [Citation(s) in RCA: 42] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2022] [Accepted: 05/01/2022] [Indexed: 11/29/2022] Open
Abstract
Cancer is a complicated disease attributed to multifactorial changes, which causes difficulties with treatment strategies. Various factors have been regarded as the main contributors, and infectious etiological factors have recently attracted interest. Several microbiomes contribute to carcinogenesis, cancer progression, and modulating cancer treatment by inducing cancerous epithelial cells and chronic inflammation. Most of our knowledge on the role of microbiota in tumor oncogenesis and clinical efficiency is associated with the intestinal microbiome. However, compelling evidence has also confirmed the contribution of the intratumor microbiome in cancer. Indeed, the findings of clinical tumor samples, animal models, and studies in vitro have revealed that many intratumor microbiomes promote tumorigenesis and immune evasion. In addition, the intratumor microbiome participates in regulating the immune response and even affects the outcomes of cancer treatment. This review summarizes the interplay between the intratumor microbiota and cancer, focusing on the contribution and mechanism of intratumor microbiota in cancer initiation, progression, and potential applications to cancer therapy.
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Affiliation(s)
- Jinyan Liu
- Biotherapy Center and Cancer Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Yi Zhang
- Biotherapy Center and Cancer Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
- State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou, Henan, China.
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Interaction of Gut Microbiota with Endocrine Homeostasis and Thyroid Cancer. Cancers (Basel) 2022; 14:cancers14112656. [PMID: 35681636 PMCID: PMC9179244 DOI: 10.3390/cancers14112656] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2022] [Revised: 05/22/2022] [Accepted: 05/24/2022] [Indexed: 01/27/2023] Open
Abstract
The gut microbiota plays a crucial role in healthy individuals as well as in patients with thyroid diseases, including thyroid cancer. Although the prognosis of differentiated thyroid cancer is predictable, that of some poorly differentiated, medullary, and anaplastic thyroid cancers remains unpromising. As the interaction between the gut microbiota and thyroid cancer has been gradually revealed in recent years, the thyroid gland, a crucial endocrine organ, is shown to have a complex connection with the body's metabolism and is involved in inflammation, autoimmunity, or cancer progression. Dysbiosis of the gut microbiota and its metabolites can influence changes in hormone levels and susceptibility to thyroid cancer through multiple pathways. In this review, we focus on the interactions of the gut microbiota with thyroid function diseases and thyroid cancer. In addition, we also discuss some potential new strategies for the prevention and treatment of thyroid disease and thyroid cancer. Our aim is to provide some possible clinical applications of gut microbiota markers for early diagnosis, treatment, and postoperative management of thyroid cancer. These findings were used to establish a better multi-disciplinary treatment and prevention management strategy and to individualize the treatment of patients in relation to their gut microbiota composition and pathological characteristics.
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Doocey CM, Finn K, Murphy C, Guinane CM. The impact of the human microbiome in tumorigenesis, cancer progression, and biotherapeutic development. BMC Microbiol 2022; 22:53. [PMID: 35151278 PMCID: PMC8840051 DOI: 10.1186/s12866-022-02465-6] [Citation(s) in RCA: 52] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Accepted: 02/03/2022] [Indexed: 02/08/2023] Open
Abstract
Abstract
Background
Cancer impacts millions of lives globally each year, with approximately 10 million cancer-related deaths recorded worldwide in 2020. Mounting research has recognised the human microbiome as a key area of interest in the pathophysiology of various human diseases including cancer tumorigenesis, progression and in disease outcome. It is suggested that approximately 20% of human cancers may be linked to microbes. Certain residents of the human microbiome have been identified as potentially playing a role, including: Helicobacter pylori, Fusobacterium nucleatum, Escherichia coli, Bacteroides fragilis and Porphyromonas gingivalis.
Main body
In this review, we explore the current evidence that indicate a link between the human microbiome and cancer. Microbiome compositional changes have been well documented in cancer patients. Furthermore, pathogenic microbes harbouring specific virulence factors have been implicated in driving the carcinogenic activity of various malignancies including colorectal, gastric and pancreatic cancer. The associated genetic mechanisms with possible roles in cancer will be outlined. It will be indicated which microbes have a potential direct link with cancer cell proliferation, tumorigenesis and disease progression. Recent studies have also linked certain microbial cytotoxins and probiotic strains to cancer cell death, suggesting their potential to target the tumour microenvironment given that cancer cells are integral to its composition. Studies pertaining to such cytotoxic activity have suggested the benefit of microbial therapies in oncological treatment regimes. It is also apparent that bacterial pathogenic protein products encoded for by certain loci may have potential as oncogenic therapeutic targets given their possible role in tumorigenesis.
Conclusion
Research investigating the impact of the human microbiome in cancer has recently gathered pace. Vast amounts of evidence indicate the human microbiome as a potential player in tumorigenesis and progression. Promise in the development of cancer biomarkers and in targeted oncological therapies has also been demonstrated, although more studies are needed. Despite extensive in vitro and in vivo research, clinical studies involving large cohorts of human patients are lacking. The current literature suggests that further intensive research is necessary to validate both the role of the human microbiome in cancer, and the use of microbiome modification in cancer therapy.
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20
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Nobuhara H, Matsugu Y, Tanaka J, Akita T, Ito K. The preventive effects of perioperative oral care on surgical site infections after pancreatic cancer surgery: a retrospective study. Support Care Cancer 2022; 30:3337-3344. [PMID: 34988706 DOI: 10.1007/s00520-021-06791-9] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2021] [Accepted: 12/30/2021] [Indexed: 11/30/2022]
Abstract
PURPOSE Pancreatic ductal adenocarcinoma (PDAC) is the most malignant cancer of the gastrointestinal system, and is associated with high rates of postoperative complications, including surgical site infections (SSIs). Perioperative oral care is an effective measure for preventing postoperative pneumonia. However, the preventive effects of perioperative oral care on SSIs have not been reported. We investigated the preventive effects of perioperative oral care on SSIs after pancreatic cancer surgery. METHODS A total of 103 patients with PDAC who underwent radical resection at Hiroshima Prefectural Hospital (2011-2018) were enrolled in this retrospective study. Of the 103 patients, 75 received perioperative oral care by dentists and dental hygienists (oral care group), whereas 28 did not (control group). Univariate and multivariate analyses with propensity score as a covariate were used to investigate the incidence and risk factors of SSIs in the oral care and control groups. RESULTS The incidence of SSIs was significantly lower in the oral care group than in the control group (12.0% vs. 39.3%, P = 0.004). Logistic regression analysis revealed that a soft pancreas, the surgical procedure (pancreaticoduodenectomy), blood transfusion, diabetes mellitus, and the absence of oral care intervention were risk factors for SSIs. The odds ratio for the absence of oral care intervention was 6.090 (95% confidence interval: 1.750-21.200, P = 0.004). CONCLUSION Our results suggest that perioperative oral care may reduce the risk of developing SSIs after pancreatic cancer surgery. These findings need to be evaluated in future prospective studies. TRIAL REGISTRATION UMIN registration number: UMIN000042082; October 15, 2020, retrospectively registered.
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Affiliation(s)
- Hiroshi Nobuhara
- Department of Dentistry, Hiroshima Prefectural Hospital, 1-5-54 Ujina-Kanda, Minami-ku, Hiroshima, 734-8530, Japan
| | - Yasuhiro Matsugu
- Department of Clinical Nutrition, Hiroshima Prefectural Hospital, 1-5-54 Ujina-Kanda, Minami-ku, Hiroshima, 734-8530, Japan. .,Department of Gastroenterological, Breast and Transplant Surgery, Hiroshima Prefectural Hospital, 1-5-54 Ujina-Kanda, Minami-ku, Hiroshima, 734-8530, Japan.
| | - Junko Tanaka
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Tomoyuki Akita
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Keiko Ito
- Department of Clinical Nutrition, Hiroshima Prefectural Hospital, 1-5-54 Ujina-Kanda, Minami-ku, Hiroshima, 734-8530, Japan
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21
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Trevisan França de Lima L, Müller Bark J, Rasheduzzaman M, Ekanayake Weeramange C, Punyadeera C. Saliva as a matrix for measurement of cancer biomarkers. Cancer Biomark 2022. [DOI: 10.1016/b978-0-12-824302-2.00008-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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22
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Sędzikowska A, Szablewski L. Human Gut Microbiota in Health and Selected Cancers. Int J Mol Sci 2021; 22:13440. [PMID: 34948234 PMCID: PMC8708499 DOI: 10.3390/ijms222413440] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2021] [Revised: 12/08/2021] [Accepted: 12/10/2021] [Indexed: 12/24/2022] Open
Abstract
The majority of the epithelial surfaces of our body, and the digestive tract, respiratory and urogenital systems, are colonized by a vast number of bacteria, archaea, fungi, protozoans, and viruses. These microbiota, particularly those of the intestines, play an important, beneficial role in digestion, metabolism, and the synthesis of vitamins. Their metabolites stimulate cytokine production by the human host, which are used against potential pathogens. The composition of the microbiota is influenced by several internal and external factors, including diet, age, disease, and lifestyle. Such changes, called dysbiosis, may be involved in the development of various conditions, such as metabolic diseases, including metabolic syndrome, type 2 diabetes mellitus, Hashimoto's thyroidis and Graves' disease; they can also play a role in nervous system disturbances, such as multiple sclerosis, Alzheimer's disease, Parkinson's disease, and depression. An association has also been found between gut microbiota dysbiosis and cancer. Our health is closely associated with the state of our microbiota, and their homeostasis. The aim of this review is to describe the associations between human gut microbiota and cancer, and examine the potential role of gut microbiota in anticancer therapy.
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Affiliation(s)
| | - Leszek Szablewski
- Chair and Department of General Biology and Parasitology, Medical University of Warsaw, ul. Chalubinskiego 5, 02-004 Warsaw, Poland;
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23
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Bacterial variation in the oral microbiota in multiple sclerosis patients. PLoS One 2021; 16:e0260384. [PMID: 34847159 PMCID: PMC8631616 DOI: 10.1371/journal.pone.0260384] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2021] [Accepted: 11/08/2021] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Microorganisms in oral cavity are called oral microbiota, while microbiome consists of total genome content of microorganisms in a host. Interaction between host and microorganisms is important in nervous system development and nervous diseases such as Autism, Alzheimer, Parkinson and Multiple Sclerosis (MS). Bacterial infections, as an environmental factor in MS pathogenesis play role in T helper 17(Th17) increase and it enhancing the production of pro-inflammatory cytokines such as Interlukin-21(IL-21), IL-17 and IL -22. Oral microbiota consists diverse populations of cultivable and uncultivable bacterial species. Denaturing gradient gel electrophoresis (DGGE) is an acceptable method for identification of uncultivable bacteria. In this study, we compared the bacterial population diversity in the oral cavity between MS and healthy people. METHODS From October to March 2019, samples were taken at Kermanshah University of Medical Sciences' MS patients center. A total of 30 samples were taken from MS patients and another 30 samples were taken from healthy people. Phenotypic tests were used to identify bacteria after pure cultures were obtained. DNA was extracted from 1 mL of saliva, and PCR products produced with primers were electrophoresed on polyacrylamide gels. RESULTS The genera Staphylococcus, Actinomyces, Fusobacterium, Bacteroides, Porphyromonas, Prevotella, Veillonella, Propionibacterium and uncultivable bacteria with accession number MW880919-25, JQ477416.1, KF074888.1 and several other un-culturable strains were significantly more abundant in the MS group while Lactobacillus and Peptostreptococcus were more prevalent in the normal healthy group according to logistic regression method. CONCLUSION Oral micro-organisms may alleviate or exacerbate inflammatory condition which impact MS disease pathogenesis. It may be assumed that controlling oral infections may result in reduction of MS disease progression.
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24
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Huang K, Wu L, Yang Y. Gut microbiota: An emerging biological diagnostic and treatment approach for gastrointestinal diseases. JGH Open 2021; 5:973-975. [PMID: 34584963 PMCID: PMC8454480 DOI: 10.1002/jgh3.12659] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Affiliation(s)
- Kun Huang
- Department of Gastroenterology Civil Aviation General Hospital Beijing China
| | - Lili Wu
- Department of Gastroenterology, The Second Medical Center Chinese PLA General Hospital Beijing China
| | - Yunsheng Yang
- Microbiota Division, Department of Gastroenterology and Hepatology, The First Medical Center Chinese PLA General Hospital Beijing China
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25
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Kunovsky L, Dite P, Jabandziev P, Dolina J, Vaculova J, Blaho M, Bojkova M, Dvorackova J, Uvirova M, Kala Z, Trna J. Helicobacter pylori infection and other bacteria in pancreatic cancer and autoimmune pancreatitis. World J Gastrointest Oncol 2021; 13:835-844. [PMID: 34457189 PMCID: PMC8371525 DOI: 10.4251/wjgo.v13.i8.835] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2021] [Revised: 03/24/2021] [Accepted: 07/05/2021] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori (H. pylori) is an infectious agent influencing as much as 50% of the world’s population. It is the causative agent for several diseases, most especially gastric and duodenal peptic ulcer, gastric adenocarcinoma and mucosa-associated lymphoid tissue lymphoma of the stomach. A number of other, extragastric manifestations also are associated with H. pylori infection. These include neurological disorders, such as Alzheimer’s disease, demyelinating multiple sclerosis and Parkinson’s disease. There is also evidence for a relationship between H. pylori infection and such dermatological diseases as psoriasis and rosacea as well as a connection with infection and open-angle glaucoma. Generally little is known about the relationship between H. pylori infection and diseases of the pancreas. Most evidence about H. pylori and its potential role in the development of pancreatic diseases concerns pancreatic adenocarcinoma and autoimmune forms of chronic pancreatitis. There is data (albeit not fully consistent) indicating modestly increased pancreatic cancer risk in H. pylori-positive patients. The pathogenetic mechanism of this increase is not yet fully elucidated, but several theories have been proposed. Reduction of antral D-cells in H. pylori-positive patients causes a suppression of somatostatin secretion that, in turn, stimulates increased secretin secretion. That stimulates pancreatic growth and thus increases the risk of carcinogenesis. Alternatively, H. pylori, as a part of microbiome dysbiosis and the so-called oncobiome, is proven to be associated with pancreatic adenocarcinoma development via the promotion of cellular proliferation. The role of H. pylori in the inflammation characteristic of autoimmune pancreatitis seems to be explained by a mechanism of molecular mimicry among several proteins (mostly enzymes) of H. pylori and pancreatic tissue. Patients with autoimmune pancreatitis often show positivity for antibodies against H. pylori proteins. H. pylori, as a part of microbiome dysbiosis, also is viewed as a potential trigger of autoimmune inflammation of the pancreas. It is precisely these relationships (and associated equivocal conclusions) that constitute a center of attention among pancreatologists, immunologists and pathologists. In order to obtain clear and valid results, more studies on sufficiently large cohorts of patients are needed. The topic is itself sufficiently significant to draw the interest of clinicians and inspire further systematic research. Next-generation sequencing could play an important role in investigating the microbiome as a potential diagnostic and prognostic biomarker for pancreatic cancer.
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Affiliation(s)
- Lumir Kunovsky
- Department of Surgery, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno 62500, Czech Republic
- Department of Gastroenterology and Internal Medicine, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno 62500, Czech Republic
| | - Petr Dite
- Department of Gastroenterology and Internal Medicine, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno 62500, Czech Republic
- Department of Gastroenterology and Internal Medicine, University Hospital Ostrava, Ostrava 70800, Czech Republic
- Faculty of Medicine, University of Ostrava, Ostrava 70300, Czech Republic
| | - Petr Jabandziev
- Department of Pediatrics, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno 61300, Czech Republic
- Central European Institute of Technology, Masaryk University, Brno 62500, Czech Republic
| | - Jiri Dolina
- Department of Gastroenterology and Internal Medicine, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno 62500, Czech Republic
| | - Jitka Vaculova
- Department of Gastroenterology and Internal Medicine, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno 62500, Czech Republic
| | - Martin Blaho
- Department of Gastroenterology and Internal Medicine, University Hospital Ostrava, Ostrava 70800, Czech Republic
- Faculty of Medicine, University of Ostrava, Ostrava 70300, Czech Republic
| | - Martina Bojkova
- Department of Gastroenterology and Internal Medicine, University Hospital Ostrava, Ostrava 70800, Czech Republic
- Faculty of Medicine, University of Ostrava, Ostrava 70300, Czech Republic
| | - Jana Dvorackova
- Department of Intensive Medicine, Emergency Medicine and Forensic Studies, University Hospital Ostrava, Ostrava 70800, Czech Republic
- Faculty of Medicine, University of Ostrava, Ostrava 70300, Czech Republic
| | | | - Zdenek Kala
- Department of Surgery, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno 62500, Czech Republic
| | - Jan Trna
- Department of Gastroenterology and Internal Medicine, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno 62500, Czech Republic
- Department of Gastroenterology and Digestive Endoscopy, Masaryk Memorial Cancer Institute, Brno 65653, Czech Republic
- Department of Internal Medicine, Hospital Boskovice, Boskovice 68001, Czech Republic
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26
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Gut microbiota in pancreatic diseases: possible new therapeutic strategies. Acta Pharmacol Sin 2021; 42:1027-1039. [PMID: 33093569 DOI: 10.1038/s41401-020-00532-0] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2020] [Accepted: 09/08/2020] [Indexed: 12/13/2022]
Abstract
Pancreatic diseases such as pancreatitis, type 1 diabetes and pancreatic cancer impose substantial health-care costs and contribute to marked morbidity and mortality. Recent studies have suggested a link between gut microbiota dysbiosis and pancreatic diseases; however, the potential roles and mechanisms of action of gut microbiota in pancreatic diseases remain to be fully elucidated. In this review, we summarize the evidence that supports relationship between alterations of gut microbiota and development of pancreatic diseases, and discuss the potential molecular mechanisms of gut microbiota dysbiosis in the pathogenesis of pancreatic diseases. We also propose current strategies toward gut microbiota to advance a developing research field that has clinical potential to reduce the cost of pancreatic diseases.
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27
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LaCourse KD, Johnston CD, Bullman S. The relationship between gastrointestinal cancers and the microbiota. Lancet Gastroenterol Hepatol 2021; 6:498-509. [PMID: 33743198 PMCID: PMC10773981 DOI: 10.1016/s2468-1253(20)30362-9] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2020] [Revised: 11/17/2020] [Accepted: 11/19/2020] [Indexed: 02/07/2023]
Abstract
The contribution of the microbiota to disease progression and treatment efficacy is often neglected when determining who is at the highest risk of developing gastrointestinal cancers or designing treatment strategies for patients. We reviewed the current literature on the effect of the human microbiota on cancer risk, prognosis, and treatment efficacy. We highlight emerging research that seeks to identify microbial signatures as biomarkers for various gastrointestinal cancers, and discuss how we could harness knowledge of the microbiome to detect, prevent, and treat these cancers. Finally, we outline further research needed in the field of gastrointestinal cancers and the microbiota, and describe the efforts required to increase the accuracy and reproducibility of data linking the microbiome to cancer.
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Affiliation(s)
- Kaitlyn D LaCourse
- Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | - Christopher D Johnston
- Vaccine and Infection Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | - Susan Bullman
- Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
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28
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Shirazi MSR, Al-Alo KZK, Al-Yasiri MH, Lateef ZM, Ghasemian A. Microbiome Dysbiosis and Predominant Bacterial Species as Human Cancer Biomarkers. J Gastrointest Cancer 2021; 51:725-728. [PMID: 31605288 DOI: 10.1007/s12029-019-00311-z] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
PURPOSE To evaluate bacterial agents as cancer biomarkers. METHODS AND RESULTS Various bacterial species have been demonstrated to involve in human cancers. However, the data is not enough for better understanding of predominant specific species. Application of a rapid and early-diagnostic, cost-effective, non-invasive, and inclusive method is a crucial approach for obtaining valid results. The role of Helicobacter pylori (H. pylori) in gastric and duodenal cancer has been confirmed. From investigation among previous publications, we attempted to make it clear which bacterial species significantly and specifically increase in various cancer types. It was unraveled that there is significant change in Granulicatella adiacens (G. adiacens) in lung cancer (LC), Fusobacterium nucleatum (F. nucleatum) in colorectal cancer (CRC), H. pylori and Porphyromonas gingivalis (P. gingivalis) in pancreatic cancer, and Streptococcus spp. in oral cancer. CONCLUSION Alteration in the cell cycle by means of different mechanisms such as inflammation, alteration in cell signaling, invasion and immune evasion, specific niche colonization, induction of DNA damage and mutation, expression of some microRNAs, and enhancing epigenetic effects are the most common mechanisms employed by bacterial species.
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Affiliation(s)
| | - K Z K Al-Alo
- Department of Veterinary Clinical Sciences, Faculty of Veterinary Medicine, University of Kufa, Kufa, Iraq
| | | | | | - Abdolmajid Ghasemian
- Department of Biology, Central Tehran Branch, Islamic Azad University, Tehran, Iran.
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29
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Janiak MC, Montague MJ, Villamil CI, Stock MK, Trujillo AE, DePasquale AN, Orkin JD, Bauman Surratt SE, Gonzalez O, Platt ML, Martínez MI, Antón SC, Dominguez-Bello MG, Melin AD, Higham JP. Age and sex-associated variation in the multi-site microbiome of an entire social group of free-ranging rhesus macaques. MICROBIOME 2021; 9:68. [PMID: 33752735 PMCID: PMC7986251 DOI: 10.1186/s40168-021-01009-w] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/03/2020] [Accepted: 02/02/2021] [Indexed: 05/07/2023]
Abstract
BACKGROUND An individual's microbiome changes over the course of its lifetime, especially during infancy, and again in old age. Confounding factors such as diet and healthcare make it difficult to disentangle the interactions between age, health, and microbial changes in humans. Animal models present an excellent opportunity to study age- and sex-linked variation in the microbiome, but captivity is known to influence animal microbial abundance and composition, while studies of free-ranging animals are typically limited to studies of the fecal microbiome using samples collected non-invasively. Here, we analyze a large dataset of oral, rectal, and genital swabs collected from 105 free-ranging rhesus macaques (Macaca mulatta, aged 1 month-26 years), comprising one entire social group, from the island of Cayo Santiago, Puerto Rico. We sequenced 16S V4 rRNA amplicons for all samples. RESULTS Infant gut microbial communities had significantly higher relative abundances of Bifidobacterium and Bacteroides and lower abundances of Ruminococcus, Fibrobacter, and Treponema compared to older age groups, consistent with a diet high in milk rather than solid foods. The genital microbiome varied widely between males and females in beta-diversity, taxonomic composition, and predicted functional profiles. Interestingly, only penile, but not vaginal, microbiomes exhibited distinct age-related changes in microbial beta-diversity, taxonomic composition, and predicted functions. Oral microbiome composition was associated with age, and was most distinctive between infants and other age classes. CONCLUSIONS Across all three body regions, with notable exceptions in the penile microbiome, while infants were distinctly different from other age groups, microbiomes of adults were relatively invariant, even in advanced age. While vaginal microbiomes were exceptionally stable, penile microbiomes were quite variable, especially at the onset of reproductive age. Relative invariance among adults, including elderly individuals, is contrary to findings in humans and mice. We discuss potential explanations for this observation, including that age-related microbiome variation seen in humans may be related to changes in diet and lifestyle. Video abstract.
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Affiliation(s)
- Mareike C Janiak
- Department of Anthropology and Archaeology, University of Calgary, Alberta, Canada.
- Alberta Children's Hospital Research Institute, Alberta, Canada.
- Department of Anthropology, New York University, New York, USA.
- School of Science, Engineering and Environment, University of Salford, Salford, UK.
| | - Michael J Montague
- Department of Neuroscience, University of Pennsylvania, Philadelphia, PA, USA
| | - Catalina I Villamil
- School of Chiropractic, Universidad Central del Caribe, Bayamón, Puerto Rico
| | - Michala K Stock
- Department of Sociology and Anthropology, Metropolitan State University of Denver, Denver, CO, USA
| | - Amber E Trujillo
- Department of Anthropology, New York University, New York, USA
- New York Consortium in Evolutionary Primatology, New York, NY, USA
| | - Allegra N DePasquale
- Department of Anthropology and Archaeology, University of Calgary, Alberta, Canada
| | - Joseph D Orkin
- Institut de Biologia Evolutiva, Universitat Pompeu Fabra-CSIC, Barcelona, Spain
| | | | - Olga Gonzalez
- Disease Intervention and Prevention, Southwest National Primate Research Center, San Antonio, TX, USA
| | - Michael L Platt
- Department of Neuroscience, University of Pennsylvania, Philadelphia, PA, USA
| | - Melween I Martínez
- Caribbean Primate Research Center, University of Puerto Rico, San Juan, Puerto Rico
| | - Susan C Antón
- Department of Anthropology, New York University, New York, USA
- New York Consortium in Evolutionary Primatology, New York, NY, USA
| | - Maria Gloria Dominguez-Bello
- Department of Biochemistry and Microbiology, Rutgers University, New Brunswick, NJ, USA
- Department of Anthropology, Rutgers University, New Brunswick, NJ, USA
| | - Amanda D Melin
- Department of Anthropology and Archaeology, University of Calgary, Alberta, Canada
- Alberta Children's Hospital Research Institute, Alberta, Canada
- Department of Medical Genetics, University of Calgary, Alberta, Canada
| | - James P Higham
- Department of Anthropology, New York University, New York, USA
- New York Consortium in Evolutionary Primatology, New York, NY, USA
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30
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Huang K, Gao X, Wu L, Yan B, Wang Z, Zhang X, Peng L, Yu J, Sun G, Yang Y. Salivary Microbiota for Gastric Cancer Prediction: An Exploratory Study. Front Cell Infect Microbiol 2021; 11:640309. [PMID: 33777850 PMCID: PMC7988213 DOI: 10.3389/fcimb.2021.640309] [Citation(s) in RCA: 57] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2020] [Accepted: 02/03/2021] [Indexed: 12/24/2022] Open
Abstract
To characterize the salivary microbiota in patients at different progressive histological stages of gastric carcinogenesis and identify microbial markers for detecting gastric cancer, two hundred and ninety-three patients were grouped into superficial gastritis (SG; n = 101), atrophic gastritis (AG; n = 93), and gastric cancer (GC; n = 99) according to their histology. 16S rRNA gene sequencing was used to access the salivary microbiota profile. A random forest model was constructed to classify gastric histological types based on the salivary microbiota compositions. A distinct salivary microbiota was observed in patients with GC when comparing with SG and AG, which was featured by an enrichment of putative proinflammatory taxa including Corynebacterium and Streptococcus. Among the significantly decreased oral bacteria in GC patients including Haemophilus, Neisseria, Parvimonas, Peptostreptococcus, Porphyromonas, and Prevotella, Haemophilus, and Neisseria are known to reduce nitrite, which may consequently result in an accumulation of carcinogenic N-nitroso compounds. We found that GC can be distinguished accurately from patients with AG and SG (AUC = 0.91) by the random forest model based on the salivary microbiota profiles, and taxa belonging to unclassified Streptophyta and Streptococcus have potential as diagnostic biomarkers for GC. Remarkable changes in the salivary microbiota functions were also detected across three histological types, and the upregulation in the isoleucine and valine is in line with a higher level of these amino acids in the gastric tumor tissues that reported by other independent studies. Conclusively, bacteria in the oral cavity may contribute gastric cancer and become new diagnostic biomarkers for GC, but further evaluation against independent clinical cohorts is required. The potential mechanisms of salivary microbiota in participating the pathogenesis of GC may include an accumulation of proinflammatory bacteria and a decline in those reducing carcinogenic N-nitroso compounds.
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Affiliation(s)
- Kun Huang
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Medical School of Chinese PLA, Beijing, China.,Department of Gastroenterology, Civil Aviation General Hospital, Beijing, China
| | - Xuefeng Gao
- Central Laboratory, Shenzhen Key Laboratory of Precision Medicine for Hematological Malignancies, Shenzhen University General Hospital, Shenzhen, China
| | - Lili Wu
- Department of Gastroenterology, The Second Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Bin Yan
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Medical School of Chinese PLA, Beijing, China
| | - Zikai Wang
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Medical School of Chinese PLA, Beijing, China
| | - Xiaomei Zhang
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Medical School of Chinese PLA, Beijing, China
| | - Lihua Peng
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Medical School of Chinese PLA, Beijing, China
| | - Jiufei Yu
- Department of Gastroenterology, Civil Aviation General Hospital, Beijing, China
| | - Gang Sun
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Medical School of Chinese PLA, Beijing, China
| | - Yunsheng Yang
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Medical School of Chinese PLA, Beijing, China
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The Role of Bacterial and Fungal Human Respiratory Microbiota in COVID-19 Patients. BIOMED RESEARCH INTERNATIONAL 2021; 2021:6670798. [PMID: 33681368 PMCID: PMC7907751 DOI: 10.1155/2021/6670798] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/18/2020] [Revised: 01/04/2021] [Accepted: 02/11/2021] [Indexed: 02/06/2023]
Abstract
Recently, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of coronavirus disease 2019 (COVID-19), has led to a worldwide pandemic with millions of infected patients. Alteration in humans' microbiota was also reported in COVID-19 patients. The alteration in human microbiota may contribute to bacterial or viral infections and affect the immune system. Moreover, human's microbiota can be altered due to SARS-CoV-2 infection, and these microbiota changes can indicate the progression of COVID-19. While current studies focus on the gut microbiota, it seems necessary to pay attention to the lung microbiota in COVID-19. This study is aimed at reviewing respiratory microbiota dysbiosis among COVID-19 patients to encourage further studies on the field for assessment of SARS-CoV-2 and respiratory microbiota interaction.
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Turanli B, Yildirim E, Gulfidan G, Arga KY, Sinha R. Current State of "Omics" Biomarkers in Pancreatic Cancer. J Pers Med 2021; 11:127. [PMID: 33672926 PMCID: PMC7918884 DOI: 10.3390/jpm11020127] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2021] [Revised: 02/08/2021] [Accepted: 02/11/2021] [Indexed: 02/06/2023] Open
Abstract
Pancreatic cancer is one of the most fatal malignancies and the seventh leading cause of cancer-related deaths related to late diagnosis, poor survival rates, and high incidence of metastasis. Unfortunately, pancreatic cancer is predicted to become the third leading cause of cancer deaths in the future. Therefore, diagnosis at the early stages of pancreatic cancer for initial diagnosis or postoperative recurrence is a great challenge, as well as predicting prognosis precisely in the context of biomarker discovery. From the personalized medicine perspective, the lack of molecular biomarkers for patient selection confines tailored therapy options, including selecting drugs and their doses or even diet. Currently, there is no standardized pancreatic cancer screening strategy using molecular biomarkers, but CA19-9 is the most well known marker for the detection of pancreatic cancer. In contrast, recent innovations in high-throughput techniques have enabled the discovery of specific biomarkers of cancers using genomics, transcriptomics, proteomics, metabolomics, glycomics, and metagenomics. Panels combining CA19-9 with other novel biomarkers from different "omics" levels might represent an ideal strategy for the early detection of pancreatic cancer. The systems biology approach may shed a light on biomarker identification of pancreatic cancer by integrating multi-omics approaches. In this review, we provide background information on the current state of pancreatic cancer biomarkers from multi-omics stages. Furthermore, we conclude this review on how multi-omics data may reveal new biomarkers to be used for personalized medicine in the future.
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Affiliation(s)
- Beste Turanli
- Department of Bioengineering, Marmara University, 34722 Istanbul, Turkey; (B.T.); (E.Y.); (G.G.)
| | - Esra Yildirim
- Department of Bioengineering, Marmara University, 34722 Istanbul, Turkey; (B.T.); (E.Y.); (G.G.)
| | - Gizem Gulfidan
- Department of Bioengineering, Marmara University, 34722 Istanbul, Turkey; (B.T.); (E.Y.); (G.G.)
| | - Kazim Yalcin Arga
- Department of Bioengineering, Marmara University, 34722 Istanbul, Turkey; (B.T.); (E.Y.); (G.G.)
- Turkish Institute of Public Health and Chronic Diseases, 34718 Istanbul, Turkey
| | - Raghu Sinha
- Department of Biochemistry and Molecular Biology, Penn State College of Medicine, Hershey, PA 17033, USA
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Abstract
ABSTRACT Microorganisms can help maintain homeostasis in humans by providing nutrition, maintaining hormone balance, and regulating inflammatory responses. In the case of imbalances, these microbes can cause various diseases, even malignancy. Pancreatic cancer (PC) is characterized by high tumor invasiveness, distant metastasis, and insensitivity to traditional chemotherapeutic drugs, and it is confirmed that PC is closely related to microorganisms. Recently, most studies based on clinical samples or case reports discussed the positive or negative relationships between microorganisms and PC. However, the specific mechanisms are blurry, especially the involved immunological pathways, and the roles of beneficial flora have usually been ignored. We reviewed studies published through September 2020 as identified using PubMed, MEDLINE, and Web of Science. We mainly introduced the traits of oral, gastrointestinal, and intratumoral microbes in PC and summarized the roles of these microbes in tumorigenesis and tumoral development through immunological pathways, in addition to illustrating the relationships between metabolic diseases with PC by microorganism. In addition, we identified microorganisms as biomarkers for early diagnosis and immunotherapy. This review will be significant for greater understanding the effect of microorganisms in PC and provide more meaningful guidance for future clinical applications.
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Affiliation(s)
- Xin Wei
- From the Department of Hepatobiliary and Pancreatic Surgery, The Second Hospital of Jilin University, Changchun
| | - Chunlei Mei
- Institute of Reproductive Health, Huazhong University of Science and Technology, Wuhan, China
| | - Xixi Li
- From the Department of Hepatobiliary and Pancreatic Surgery, The Second Hospital of Jilin University, Changchun
| | - Yingjun Xie
- From the Department of Hepatobiliary and Pancreatic Surgery, The Second Hospital of Jilin University, Changchun
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Yu Q, Jobin C, Thomas RM. Implications of the microbiome in the development and treatment of pancreatic cancer: Thinking outside of the box by looking inside the gut. Neoplasia 2021; 23:246-256. [PMID: 33418277 PMCID: PMC7804346 DOI: 10.1016/j.neo.2020.12.008] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2020] [Revised: 12/23/2020] [Accepted: 12/23/2020] [Indexed: 12/19/2022]
Abstract
Pancreatic ductal adenocarcinoma is the third leading cause of cancer-related death in the United States. As one of the most lethal cancer types, the prognosis for patients diagnosed with pancreatic cancer remains dismal and novel investigations are urgently needed. Evidence for an association of microbes with pancreatic cancer risk, development, treatment response, and post-treatment survivorship is rapidly developing. Herein, we provide an overview on the role of the microbiome as it relates to the natural history of pancreatic cancer, including host immune interactions, alterations in metabolism, direct carcinogenic effect, and its role in treatment response.
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Affiliation(s)
- Qin Yu
- Department of Medicine, University of Florida College of Medicine, Gainesville, FL, USA
| | - Christian Jobin
- Department of Medicine, University of Florida College of Medicine, Gainesville, FL, USA; Department of Infectious Diseases and Immunology, University of Florida College of Medicine, Gainesville, FL, USA; Department of Anatomy and Cell Biology, University of Florida College of Medicine, Gainesville, FL, USA
| | - Ryan M Thomas
- Department of Surgery, University of Florida College of Medicine, Gainesville, FL, USA; Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, FL, USA.
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35
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Zanini S, Renzi S, Limongi AR, Bellavite P, Giovinazzo F, Bermano G. A review of lifestyle and environment risk factors for pancreatic cancer. Eur J Cancer 2021; 145:53-70. [PMID: 33423007 DOI: 10.1016/j.ejca.2020.11.040] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2020] [Revised: 11/04/2020] [Accepted: 11/24/2020] [Indexed: 12/12/2022]
Abstract
Pancreatic cancer (PaCa) is one of the deadliest cancers known and its incidence is increasing in the developed countries. Because of the lack of biomarkers that allow early detection and the tendency of the disease to be asymptomatic, the diagnosis comes often too late for effective surgical or chemotherapy intervention. Lifestyle factors, that may cause common genetic modifications occurring in the disease, interfere with pancreatic physiology or function, and play a role in PaCa development, have been of concern recently, since a strategy to prevent this severe cancer is needed. This review identifies the latest evidences related to increased risk of developing PaCa due to dietary habits such as high alcohol, fructose and red or processed meat intake, and pathological conditions such as diabetes, obesity and infections in addition to stress and smoking behaviour. It aims to highlight the importance of intervening on modifiable risk factors: the action on these factors could prevent a considerable number of new cases of PaCa.
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Affiliation(s)
- Sara Zanini
- Centre for Obesity Research and Education [CORE], School of Pharmacy & Life Sciences, Robert Gordon University, Aberdeen, UK
| | - Serena Renzi
- Centre for Obesity Research and Education [CORE], School of Pharmacy & Life Sciences, Robert Gordon University, Aberdeen, UK
| | - Antonina R Limongi
- Department of Science, University of Basilicata, Potenza, Italy; BioInnova Srl, Potenza, Italy
| | - Paolo Bellavite
- Department of Medicine, Section of General Pathology, University of Verona, Italy
| | | | - Giovanna Bermano
- Centre for Obesity Research and Education [CORE], School of Pharmacy & Life Sciences, Robert Gordon University, Aberdeen, UK.
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36
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Pancreatic Diseases and Microbiota: A Literature Review and Future Perspectives. J Clin Med 2020; 9:jcm9113535. [PMID: 33139601 PMCID: PMC7692447 DOI: 10.3390/jcm9113535] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2020] [Revised: 10/28/2020] [Accepted: 10/30/2020] [Indexed: 12/12/2022] Open
Abstract
Gut microbiota represent an interesting worldwide research area. Several studies confirm that microbiota has a key role in human diseases, both intestinal (such as inflammatory bowel disease, celiac disease, intestinal infectious diseases, irritable bowel syndrome) and extra intestinal disorders (such as autism, multiple sclerosis, rheumatologic diseases). Nowadays, it is possible to manipulate microbiota by administering prebiotics, probiotics or synbiotics, through fecal microbiota transplantation in selected cases. In this scenario, pancreatic disorders might be influenced by gut microbiota and this relationship could be an innovative and inspiring field of research. However, data are still scarce and controversial. Microbiota manipulation could represent an important therapeutic strategy in the pancreatic diseases, in addition to standard therapies. In this review, we analyze current knowledge about correlation between gut microbiota and pancreatic diseases, by discussing on the one hand existing data and on the other hand future possible perspectives.
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Li P, Shu Y, Gu Y. The potential role of bacteria in pancreatic cancer: a systematic review. Carcinogenesis 2020; 41:397-404. [PMID: 32034405 DOI: 10.1093/carcin/bgaa013] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2019] [Revised: 01/18/2020] [Accepted: 02/06/2020] [Indexed: 02/06/2023] Open
Abstract
Pancreatic cancer is a lethal and devastating disease in the worldwide. Recognized risk factors for pancreatic cancer include cigarette smoking, obesity, type II diabetes and chronic pancreatitis. Other factors such as variant ABO blood type and Helicobacter pylori may also play an important role in pancreatic carcinogenesis. Recently, growing evidence suggests that the association between bacteria and pancreatic cancer is positive and related immune/inflammation activation and increased nitrosamine exposure may be its potential mechanism. Interestingly, it is debatable whether the relationship of bacteria and pancreatic cancer is causative, reactive or parallel and future studies are in progress. Here we review recent progress in pancreatic cancer and its related bacteria.
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Affiliation(s)
- Ping Li
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Yongqian Shu
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Yanhong Gu
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
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38
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Gheorghe G, Bungau S, Ilie M, Behl T, Vesa CM, Brisc C, Bacalbasa N, Turi V, Costache RS, Diaconu CC. Early Diagnosis of Pancreatic Cancer: The Key for Survival. Diagnostics (Basel) 2020; 10:869. [PMID: 33114412 PMCID: PMC7694042 DOI: 10.3390/diagnostics10110869] [Citation(s) in RCA: 54] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2020] [Revised: 10/16/2020] [Accepted: 10/23/2020] [Indexed: 02/07/2023] Open
Abstract
Pancreatic cancer (PC) is one of the most aggressive forms of cancer. Negative prognosis is mainly due to the late diagnosis in advanced stages, when the disease is already therapeutically overcome. Studies in recent years have focused on identifying biomarkers that could play a role in early diagnosis, leading to the improvement of morbidity and mortality. Currently, the only biomarker widely used in the diagnosis of PC is carbohydrate antigen 19-9 (CA19.9), which has, however, more of a prognostic role in the follow-up of postoperative recurrence than a diagnostic role. Other biomarkers, recently identified as the methylation status of ADAMTS1 (A disintegrin and metalloproteinase with thrombospondin motifs 1) and BNC1 (zinc finger protein basonuclin-1) in cell-free deoxyribonucleic acid (DNA), may play a role in the early detection of PC. This review focuses on the diagnosis of PC in its early stages.
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Affiliation(s)
- Gina Gheorghe
- Department 5, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania; (G.G.); (M.I.); (R.S.C.)
- Department of Internal Medicine, Clinical Emergency Hospital of Bucharest, 105402 Bucharest, Romania
| | - Simona Bungau
- Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, 410028 Oradea, Romania
| | - Madalina Ilie
- Department 5, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania; (G.G.); (M.I.); (R.S.C.)
- Department of Gastroenterology, Clinical Emergency Hospital of Bucharest, 105402 Bucharest, Romania
| | - Tapan Behl
- Chitkara College of Pharmacy, Chitkara University, Punjab 140401, India;
| | - Cosmin Mihai Vesa
- Department of Preclinical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410041 Oradea, Romania;
| | - Ciprian Brisc
- Department of Medical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410041 Oradea, Romania;
| | - Nicolae Bacalbasa
- Department of Surgery, “Ion Cantacuzino” Clinical Hospital, 030167 Bucharest, Romania;
- Department 13, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania
| | - Vladiana Turi
- Department of Cardiology, “Victor Babeş” University of Medicine and Pharmacy, 300041 Timisoara, Romania;
| | - Raluca Simona Costache
- Department 5, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania; (G.G.); (M.I.); (R.S.C.)
- Department of Gastroenterology, “Carol Davila” University Emergency Central Military Hospital, 010825 Bucharest, Romania
| | - Camelia Cristina Diaconu
- Department 5, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania; (G.G.); (M.I.); (R.S.C.)
- Department of Internal Medicine, Clinical Emergency Hospital of Bucharest, 105402 Bucharest, Romania
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Kamarajan P, Ateia I, Shin JM, Fenno JC, Le C, Zhan L, Chang A, Darveau R, Kapila YL. Periodontal pathogens promote cancer aggressivity via TLR/MyD88 triggered activation of Integrin/FAK signaling that is therapeutically reversible by a probiotic bacteriocin. PLoS Pathog 2020; 16:e1008881. [PMID: 33002094 PMCID: PMC7529280 DOI: 10.1371/journal.ppat.1008881] [Citation(s) in RCA: 75] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2020] [Accepted: 08/12/2020] [Indexed: 12/13/2022] Open
Abstract
Epidemiological studies reveal significant associations between periodontitis and oral cancer. However, knowledge about the contribution of periodontal pathogens to oral cancer and potential regulatory mechanisms involved is limited. Previously, we showed that nisin, a bacteriocin and commonly used food preservative, reduced oral cancer tumorigenesis and extended the life expectancy in tumor-bearing mice. In addition, nisin has antimicrobial effects on key periodontal pathogens. Thus, the purpose of this study was to test the hypothesis that key periodontal pathogens (Porphyromonas gingivalis, Treponema denticola, and Fusobacterium nucleatum) promote oral cancer via specific host-bacterial interactions, and that bacteriocin/nisin therapy may modulate these responses. All three periodontal pathogens enhanced oral squamous cell carcinoma (OSCC) cell migration, invasion, tumorsphere formation, and tumorigenesis in vivo, without significantly affecting cell proliferation or apoptosis. In contrast, oral commensal bacteria did not affect OSCC cell migration. Pathogen-enhanced OSCC cell migration was mediated via integrin alpha V and FAK activation, since stably blocking alpha V or FAK expression abrogated these effects. Nisin inhibited these pathogen-mediated processes. Further, Treponema denticola induced TLR2 and 4 and MyD88 expression. Stable suppression of MyD88 significantly inhibited Treponema denticola-induced FAK activation and abrogated pathogen-induced migration. Together, these data demonstrate that periodontal pathogens contribute to a highly aggressive cancer phenotype via crosstalk between TLR/MyD88 and integrin/FAK signaling. Nisin can modulate these pathogen-mediated effects, and thus has therapeutic potential as an antimicrobial and anti-tumorigenic agent.
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Affiliation(s)
- Pachiyappan Kamarajan
- Department of Orofacial Sciences, School of Dentistry, University of California, San Francisco, CA, United States of America
- Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, MI, United States of America
| | - Islam Ateia
- Department of Oral Medicine and Periodontology, Mansoura University, Mansoura, Egypt
| | - Jae M. Shin
- Department of Cariology, Restorative Sciences, and Endodontics, School of Dentistry, University of Michigan, Ann Arbor, MI, United States of America
- Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, United States of America
| | - J. Christopher Fenno
- Biologic and Materials Sciences, School of Dentistry, University of Michigan, Ann arbor, MI, United States of America
| | - Charles Le
- Department of Orofacial Sciences, School of Dentistry, University of California, San Francisco, CA, United States of America
| | - Ling Zhan
- Department of Orofacial Sciences, School of Dentistry, University of California, San Francisco, CA, United States of America
| | - Ana Chang
- Department of Periodontics, Oral Health Sciences, School of Dentistry, University of Washington, Seattle, WA, United States of America
| | - Richard Darveau
- Department of Periodontics, Oral Health Sciences, School of Dentistry, University of Washington, Seattle, WA, United States of America
| | - Yvonne L. Kapila
- Department of Orofacial Sciences, School of Dentistry, University of California, San Francisco, CA, United States of America
- Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, MI, United States of America
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40
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Wu J, Zhang C, Xu S, Xiang C, Wang R, Yang D, Lu B, Shi L, Tong R, Teng Y, Dong W, Zhang J. Fecal Microbiome Alteration May Be a Potential Marker for Gastric Cancer. DISEASE MARKERS 2020; 2020:3461315. [PMID: 33014185 PMCID: PMC7519184 DOI: 10.1155/2020/3461315] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/24/2019] [Revised: 08/08/2020] [Accepted: 08/31/2020] [Indexed: 12/13/2022]
Abstract
Although intestinal microbial dysbiosis was confirmed to be associated with many chronic diseases and health status through complicated interaction with the host, the effect on gastric cancer was less studied. In this study, we sequenced the 16S rRNA and 18S rRNA genes of fecal bacteria and fungi, respectively, in 134 gastric cancer patients and 58 healthy controls matched by age and gender. Propensity score matching (PSM) was adopted for adjusting diet habits and lifestyle, and 44 patients and 44 healthy controls (matching population) were enrolled. Serum antibody to H. pylori and metabolites of the matching population were detected. The positive rates of antibody to H. pylori between the patients and the control group did not reach the statistical difference. LEfSe analysis indicated that bacteria were more stable than fungi when adjusting diet and lifestyle. Veillonella, Megasphaera, and Prevotella 7 genus and Streptococcus salivarius subsp. Salivarius, Bifidobacterium dentium, and Lactobacillus salivarius species in bacteria were related to the risk of gastric cancer and showed a good diagnostic value in distinguishing the patients from healthy controls. Streptococcus mitis showed a risk effect for gastric cancer; however, the effect turned into be protective after PSM. Serum L-alanine, L-threonine, and methionol were positively associated with Veillonella and Streptococcus and several fungi genus. Overall, our findings indicated that fecal microbiome constitution alteration may be associated with gastric cancer through influencing the amino acid metabolism.
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Affiliation(s)
- Juan Wu
- School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Cong Zhang
- School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Shuo Xu
- School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Chunjie Xiang
- School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Ruiping Wang
- Department of Oncology, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing, China
| | - Dongqing Yang
- School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Bin Lu
- Department of Oncology, Yangzhong People's Hospital, Yangzhong, China
| | - Liyun Shi
- School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Ruimin Tong
- Department of Oncology, Yangzhong People's Hospital, Yangzhong, China
| | - Yuhao Teng
- Department of Oncology, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing, China
| | - Wei Dong
- School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Junfeng Zhang
- School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, China
- Jiangsu Collaborative Innovation Center Medicine (TCM) Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, Nanjing, China
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41
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Arteta AA, Milanes-Yearsley M, Cardona-Castro N. Cholangiocyte derived carcinomas and local microbiota. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2020; 29:1084-1093. [PMID: 32902144 DOI: 10.1002/jhbp.826] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/19/2020] [Revised: 08/10/2020] [Accepted: 08/11/2020] [Indexed: 02/06/2023]
Abstract
Trillions of bacteria are present in the gastrointestinal tract as part of the local microbiota. Bacteria have been associated with a wide range of gastrointestinal diseases including malignant neoplasms. The association of bacteria in gastrointestinal and biliary tract carcinogenesis is supported in the paradigm of Helicobacter pylori and intestinal-type gastric cancer. However, the association of bacterial species to a specific carcinoma, different from intestinal-type gastric cancer is unresolved. The relationship of bacteria to a specific malignant neoplasm can drive clinical interventions. We review the classic bacteria risk factors identified using cultures and PCR (polymerase chain reaction) with new research regarding a microbiota approach through 16S rRNA (16S ribosomal ribonucleic acid gene) or metagenomic analysis for selected carcinomas in the biliary tract.
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Affiliation(s)
- Ariel A Arteta
- Department of Pathology, University of Antioquia, Medellín, Colombia.,Basic Science Research Group, School of Medicine, CES University, Medellín (Antioquia), Colombia.,Grupo de Investigaciones en Patología, Universidad de Antioquia (GRIP-UdeA), Medellín (Antioquia), Colombia
| | - Martha Milanes-Yearsley
- Ohio State University, Columbus, OH, USA.,Gastrointestinal and Liver Pathology Department, Wexner Medical Center, Columbus, OH, USA
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Relationship between the Oral and Vaginal Microbiota of South African Adolescents with High Prevalence of Bacterial Vaginosis. Microorganisms 2020; 8:microorganisms8071004. [PMID: 32635588 PMCID: PMC7409319 DOI: 10.3390/microorganisms8071004] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2020] [Revised: 06/18/2020] [Accepted: 06/28/2020] [Indexed: 01/01/2023] Open
Abstract
Bacterial vaginosis (BV) and periodontal disease (PD) are characterised as bacterial dysbioses. Both are associated with an increased risk of poor pregnancy outcomes, yet it is unknown whether PD and BV are related. We characterised the oral microbiota of young South African females with a high prevalence of BV and investigated the association between oral communities and vaginal microbiota. DNA was extracted from vaginal lateral wall, saliva and supragingival plaque samples from 94 adolescent females (aged 15–19 years). 16S rRNA gene sequencing of the V4 hypervariable region was performed for analysis of the oral and vaginal microbiota and BV status was determined by Nugent scoring. The core oral microbiota was predominately comprised of Firmicutes followed by Proteobacteria and Bacteroidetes. The salivary microbiota of participants with BV was more diverse than those with lactobacillus-dominated communities (p = 0.030). PD-associated bacterial species, including Prevotella intermedia and Porphyromonas endodontalis were enriched in the supragingival microbiota of women with non-optimal vaginal communities compared to those with Lactobacillus-dominant communities, while Pseudomonas aeruginosa and Prevotella intermedia were enriched in the saliva of women with non-optimal vaginal microbiota. These data suggest a relationship between oral and vaginal dysbiosis, warranting further investigation into whether they are casually related.
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43
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Elsalem L, Jum'ah AA, Alfaqih MA, Aloudat O. The Bacterial Microbiota of Gastrointestinal Cancers: Role in Cancer Pathogenesis and Therapeutic Perspectives. Clin Exp Gastroenterol 2020; 13:151-185. [PMID: 32440192 PMCID: PMC7211962 DOI: 10.2147/ceg.s243337] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2019] [Accepted: 04/13/2020] [Indexed: 12/24/2022] Open
Abstract
The microbiota has an essential role in the pathogenesis of many gastrointestinal diseases including cancer. This effect is mediated through different mechanisms such as damaging DNA, activation of oncogenic pathways, production of carcinogenic metabolites, stimulation of chronic inflammation, and inhibition of antitumor immunity. Recently, the concept of "pharmacomicrobiomics" has emerged as a new field concerned with exploring the interplay between drugs and microbes. Mounting evidence indicates that the microbiota and their metabolites have a major impact on the pharmacodynamics and therapeutic responses toward anticancer drugs including conventional chemotherapy and molecular-targeted therapeutics. In addition, microbiota appears as an attractive target for cancer prevention and treatment. In this review, we discuss the role of bacterial microbiota in the pathogenesis of different cancer types affecting the gastrointestinal tract system. We also scrutinize the evidence regarding the role of microbiota in anticancer drug responses. Further, we discuss the use of probiotics, fecal microbiota transplantation, and antibiotics, either alone or in combination with anticancer drugs for prevention and treatment of gastrointestinal tract cancers.
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Affiliation(s)
- Lina Elsalem
- Department of Pharmacology, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan
| | - Ahmad A Jum'ah
- Department of Conservative Dentistry, Faculty of Dentistry, Jordan University of Science and Technology, Irbid, Jordan
| | - Mahmoud A Alfaqih
- Department of Physiology and Biochemistry, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan
| | - Osama Aloudat
- Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan
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El Bairi K, Jabi R, Trapani D, Boutallaka H, Ouled Amar Bencheikh B, Bouziane M, Amrani M, Afqir S, Maleb A. Can the microbiota predict response to systemic cancer therapy, surgical outcomes, and survival? The answer is in the gut. Expert Rev Clin Pharmacol 2020; 13:403-421. [PMID: 32308061 DOI: 10.1080/17512433.2020.1758063] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2019] [Accepted: 04/16/2020] [Indexed: 02/06/2023]
Abstract
INTRODUCTION The gut microbiota seems to play a key role in tumorigenesis, across various hallmarks of cancer. Recent evidence suggests its potential use as a biomarker predicting drug response and adding prognostic information, generally in the context of immuno-oncology. AREAS COVERED In this review, we focus on the modulating effects of gut microbiota dysbiosis on various anticancer molecules used in practice, including cytotoxic and immune-modulating agents, primarily immune-checkpoint inhibitors (ICI). Pubmed/Medline-based literature search was conducted to find potential original studies that discuss gut microbiota as a prognostic and predictive biomarker for cancer therapy. We also looked at the US ClinicalTrials.gov website to find additional studies particularly ongoing human clinical trials. EXPERT COMMENTARY Sequencing of stool-derived materials and tissue samples from cancer patients and animal models has shown a significant enrichment of various bacteria such as Fusobacterium nucleatum and Bacteroides fragilis were associated with resistant disease and poorer outcomes. Gut microbiota was also found to be associated with surgical outcomes and seems to play a significant role in anastomotic leak (ATL) after surgery mainly by collagen breakdown. However, this research field is just at the beginning and the current findings are not yet ready to change clinical practice.
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Affiliation(s)
- Khalid El Bairi
- Cancer Biomarkers Working Group, Mohamed Ist University , Oujda, Morocco
- Faculty of Medicine and Pharmacy, Mohamed Ist University , Oujda, Morocco
| | - Rachid Jabi
- Faculty of Medicine and Pharmacy, Mohamed Ist University , Oujda, Morocco
- Department of Visceral Surgery, Mohamed VI University Hospital , Oujda, Morocco
| | - Dario Trapani
- Department of Haematology and Oncology, European Institute of Oncology, IEO, IRCCS, University of Milano , Milan, Italy
| | - Hanae Boutallaka
- Department of Gastroenterology and Digestive Endoscopy, Mohamed V Military Teaching Hospital of Rabat, Mohamed V University , Rabat, Morocco
| | | | - Mohammed Bouziane
- Faculty of Medicine and Pharmacy, Mohamed Ist University , Oujda, Morocco
- Department of Visceral Surgery, Mohamed VI University Hospital , Oujda, Morocco
| | - Mariam Amrani
- Department of Pathology, National Institute of Oncology, Faculty of Medicine and Pharmacy, Mohamed V University , Rabat, Morocco
| | - Said Afqir
- Cancer Biomarkers Working Group, Mohamed Ist University , Oujda, Morocco
- Faculty of Medicine and Pharmacy, Mohamed Ist University , Oujda, Morocco
- Department of Medical Oncology, Mohamed VI University Hospital , Oujda, Morocco
| | - Adil Maleb
- Faculty of Medicine and Pharmacy, Mohamed Ist University , Oujda, Morocco
- Department of Microbiology, Mohamed VI University Hospital , Oujda, Morocco
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Sollie S, Santaolalla A, Michaud DS, Sarker D, Karagiannis SN, Josephs DH, Hammar N, Walldius G, Garmo H, Holmberg L, Jungner I, Van Hemelrijck M. Serum Immunoglobulin G Is Associated With Decreased Risk of Pancreatic Cancer in the Swedish AMORIS Study. Front Oncol 2020; 10:263. [PMID: 32185133 PMCID: PMC7059192 DOI: 10.3389/fonc.2020.00263] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2019] [Accepted: 02/14/2020] [Indexed: 12/15/2022] Open
Abstract
Background: Emerging evidence points to potential roles of the humoral immune responses in the development of pancreatic cancer. Epidemiological studies have suggested involvement of viral and bacterial infections in pancreatic carcinogenesis. Experimental studies have reported high expression levels of antigens in pancreatic cancer cells. Therefore, we aimed to investigate the role of different components of humoral immunity in the context of pancreatic cancer. We evaluated associations between pre-diagnostic serum markers of the overall humoral immune system [immunoglobulin A (IgA), immunoglobulin G (IgG) and immunoglobulin M (IgM)], and the risk of pancreatic cancer in the Swedish Apolipoprotein-related MORtality RISk (AMORIS) study. Methods: We selected all participants (≥20 years old) with baseline measurements of IgA, IgG or IgM (n = 41,900, 136,221, and 29,919, respectively). Participants were excluded if they had a history of chronic pancreatitis and individuals were free from pancreatic cancer at baseline. Multivariate Cox proportional hazards regression was used to estimate risk of pancreatic cancer for medical cut-offs of IgA, IgG, and IgM. Results: Compared to the reference level of 6.10–14.99 g/L, risk of pancreatic cancer was elevated among those with IgG levels <6.10 g/L [HR: 1.69 (95% CI 0.99–2.87)], and an inverse association was observed among those with IgG levels ≥15.00 g/L [0.82 (95% CI 0.64–1.05); Ptrend = 0.027]. The association appeared to be stronger for women than men [HR: 0.64 (95% CI 0.43–0.97) and 0.95 (95% CI 0.69–1.29), respectively]. No associations were observed with IgA or IgM. Conclusion: An inverse association was observed between pre-diagnostic serum levels of IgG and risk of pancreatic cancer. Our findings highlight the need to further investigate the role of immune response in pancreatic cancer etiology.
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Affiliation(s)
- Sam Sollie
- Translational Oncology & Urology Research (TOUR), School of Cancer and Pharmaceutical Sciences, King's College London, London, United Kingdom
| | - Aida Santaolalla
- Translational Oncology & Urology Research (TOUR), School of Cancer and Pharmaceutical Sciences, King's College London, London, United Kingdom
| | - Dominique S Michaud
- Department of Public Health and Community Medicine, Tufts University School of Medicine, Boston, MA, United States.,Department of Epidemiology, Brown University School of Public Health, Providence, RI, United States
| | - Debashis Sarker
- Translational Oncology & Urology Research (TOUR), School of Cancer and Pharmaceutical Sciences, King's College London, London, United Kingdom.,Department of Medical Oncology, Guy's and St Thomas' NHS Trust, London, United Kingdom
| | - Sophia N Karagiannis
- St John's Institute of Dermatology, School of Basic and Medical Biosciences, King's College London, Guy's Hospital, London, United Kingdom
| | - Debra H Josephs
- Translational Oncology & Urology Research (TOUR), School of Cancer and Pharmaceutical Sciences, King's College London, London, United Kingdom.,Department of Medical Oncology, Guy's and St Thomas' NHS Trust, London, United Kingdom
| | - Niklas Hammar
- Unit of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Goran Walldius
- Unit of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Hans Garmo
- Translational Oncology & Urology Research (TOUR), School of Cancer and Pharmaceutical Sciences, King's College London, London, United Kingdom
| | - Lars Holmberg
- Translational Oncology & Urology Research (TOUR), School of Cancer and Pharmaceutical Sciences, King's College London, London, United Kingdom
| | - Ingmar Jungner
- Clinical Epidemiological Unit, Department of Medicine, Karolinska Institutet and CALAB Research, Stockholm, Sweden
| | - Mieke Van Hemelrijck
- Translational Oncology & Urology Research (TOUR), School of Cancer and Pharmaceutical Sciences, King's College London, London, United Kingdom.,Unit of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
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Balanced oral pathogenic bacteria and probiotics promoted wound healing via maintaining mesenchymal stem cell homeostasis. Stem Cell Res Ther 2020; 11:61. [PMID: 32059742 PMCID: PMC7023757 DOI: 10.1186/s13287-020-1569-2] [Citation(s) in RCA: 49] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2019] [Revised: 01/13/2020] [Accepted: 01/22/2020] [Indexed: 12/15/2022] Open
Abstract
Objectives The homeostasis of oral pathogenic bacteria and probiotics plays a crucial role in maintaining the well-being and healthy status of human host. Our previous study confirmed that imbalanced oral microbiota could impair mesenchymal stem cell (MSC) proliferation capacity and delay wound healing. However, the effects of balanced oral pathogenic bacteria and probiotics on MSCs and wound healing are far from clear. Here, the balance of pathogenic bacteria Porphyromonas gingivalis and probiotics Lactobacillus reuteri extracts was used to investigate whether balanced oral microbiota modulate the physiological functions of MSCs and promote wound healing. Methods The effects of balanced pathogenic bacteria P. gingivalis and probiotics L. reuteri extracts on gingival MSCs (GMSCs) were tested using the migration, alkaline phosphatase activity, alizarin red staining, cell counting kit-8, real-time PCR, and western blot assays. To investigate the role of balanced pathogenic bacteria P. gingivalis and probiotics L. reuteri extracts in the wound of mice, the wounds were established in the mucosa of palate and were inoculated with bacteria every 2 days. Results We found that the balance between pathogenic bacteria and probiotics enhanced the migration, osteogenic differentiation, and cell proliferation of MSCs. Additionally, local inoculation of the mixture of L. reuteri and P. gingivalis promoted the process of wound healing in mice. Mechanistically, we found that LPS in P. gingivalis could activate NLRP3 inflammasome and inhibit function of MSCs, thereby accelerating MSC dysfunction and delaying wound healing. Furthermore, we also found that reuterin was the effective ingredient in L. reuteri which maintained the balance of pathogenic bacteria and probiotics by neutralizing LPS in P. gingivalis, thus inhibiting inflammation and promoting wound healing. Conclusions This study revealed that the homeostasis of oral microbiomes played an indispensable role in maintaining oral heath, provided hopeful methods for the prevention and treatment of oral diseases, and had some referential value for other systemic diseases caused by dysfunction of microbiota and MSCs.
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Wang Y, Yang G, You L, Yang J, Feng M, Qiu J, Zhao F, Liu Y, Cao Z, Zheng L, Zhang T, Zhao Y. Role of the microbiome in occurrence, development and treatment of pancreatic cancer. Mol Cancer 2019; 18:173. [PMID: 31785619 PMCID: PMC6885316 DOI: 10.1186/s12943-019-1103-2] [Citation(s) in RCA: 76] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2019] [Accepted: 11/12/2019] [Indexed: 02/06/2023] Open
Abstract
Pancreatic cancer is one of the most lethal malignancies. Recent studies indicated that development of pancreatic cancer may be intimately connected with the microbiome. In this review, we discuss the mechanisms through which microbiomes affect the development of pancreatic cancer, including inflammation and immunomodulation. Potential therapeutic and diagnostic applications of microbiomes are also discussed. For example, microbiomes may serve as diagnostic markers for pancreatic cancer, and may also play an important role in determining the efficacies of treatments such as chemo- and immunotherapies. Future studies will provide additional insights into the various roles of microbiomes in pancreatic cancer.
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Affiliation(s)
- Yicheng Wang
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujing Street, Beijing, 100730 China
| | - Gang Yang
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujing Street, Beijing, 100730 China
| | - Lei You
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujing Street, Beijing, 100730 China
| | - Jinshou Yang
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujing Street, Beijing, 100730 China
| | - Mengyu Feng
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujing Street, Beijing, 100730 China
| | - Jiangdong Qiu
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujing Street, Beijing, 100730 China
| | - Fangyu Zhao
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujing Street, Beijing, 100730 China
| | - Yueze Liu
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujing Street, Beijing, 100730 China
| | - Zhe Cao
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujing Street, Beijing, 100730 China
| | - Lianfang Zheng
- Department of Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730 China
| | - Taiping Zhang
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujing Street, Beijing, 100730 China
- Clinical Immunology Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730 China
| | - Yupei Zhao
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujing Street, Beijing, 100730 China
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Wei MY, Shi S, Liang C, Meng QC, Hua J, Zhang YY, Liu J, Zhang B, Xu J, Yu XJ. The microbiota and microbiome in pancreatic cancer: more influential than expected. Mol Cancer 2019; 18:97. [PMID: 31109338 PMCID: PMC6526613 DOI: 10.1186/s12943-019-1008-0] [Citation(s) in RCA: 184] [Impact Index Per Article: 30.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2019] [Accepted: 03/19/2019] [Indexed: 12/12/2022] Open
Abstract
Microbiota is just beginning to be recognized as an important player in carcinogenesis and the interplay among microbes is greater than expected. Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease for which mortality closely parallels incidence. Early detection would provide the best opportunity to increase survival rates. Specific well-studied oral, gastrointestinal, and intrapancreatic microbes and some kinds of hepatotropic viruses and bactibilia may have potential etiological roles in pancreatic carcinogenesis, or modulating individual responses to oncotherapy. Concrete mechanisms mainly involve perpetuating inflammation, regulating the immune system-microbe-tumor axis, affecting metabolism, and altering the tumor microenvironment. The revolutionary technology of omics has generated insight into cancer microbiomes. A better understanding of the microbiota in PDAC might lead to the establishment of screening or early-stage diagnosis methods, implementation of cancer bacteriotherapy, adjustment of therapeutic efficacy even alleviating the adverse effects, creating new opportunities and fostering hope for desperate PDAC patients.
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Affiliation(s)
- Miao-Yan Wei
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032 China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032 China
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032 China
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032 China
| | - Si Shi
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032 China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032 China
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032 China
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032 China
| | - Chen Liang
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032 China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032 China
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032 China
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032 China
| | - Qing-Cai Meng
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032 China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032 China
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032 China
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032 China
| | - Jie Hua
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032 China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032 China
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032 China
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032 China
| | - Yi-Yin Zhang
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032 China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032 China
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032 China
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032 China
| | - Jiang Liu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032 China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032 China
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032 China
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032 China
| | - Bo Zhang
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032 China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032 China
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032 China
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032 China
| | - Jin Xu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032 China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032 China
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032 China
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032 China
| | - Xian-Jun Yu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032 China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032 China
- Pancreatic Cancer Institute, Fudan University, Shanghai, 200032 China
- Shanghai Pancreatic Cancer Institute, Shanghai, 200032 China
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Dysregulated Phosphate Metabolism, Periodontal Disease, and Cancer: Possible Global Health Implications. Dent J (Basel) 2019; 7:dj7010018. [PMID: 30754693 PMCID: PMC6473307 DOI: 10.3390/dj7010018] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2018] [Revised: 01/31/2019] [Accepted: 02/06/2019] [Indexed: 01/08/2023] Open
Abstract
An association between periodontal disease and cancer has been established in recent studies, but no common etiology has been identified in the hopes of reducing the global burden of these non-communicable diseases. This perspective article hypothesizes that the determinant mediating the association of periodontal disease with cancer is dysregulated phosphate metabolism. Phosphate, an essential dietary micronutrient, is dysregulated in chronic kidney disease, and both cancer and periodontal disease are associated with chronic kidney disease. Reviewed evidence includes the association between phosphate toxicity and cancer development, and the association between periodontal disease and chronic kidney disease-mineral and bone disorder includes conditions such as ectopic calcification and bone resorption, which may be indirectly related to periodontal disease. Dental calculus in periodontal disease contains calcium phosphate crystals that are deposited from excess calcium and phosphate in saliva. Alveolar bone resorption may be linked systemically to release of parathyroid hormone in response to hypocalcemia induced by hyperphosphatemia. More research is needed to examine the role of dysregulated phosphate metabolism in periodontal disease.
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